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Genetically modified animals are animals that have been
genetically modified Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including ...
for a variety of purposes including producing drugs, enhancing yields, increasing resistance to disease, etc. The vast majority of genetically modified animals are at the research stage while the number close to entering the market remains small.


Production

The process of genetically engineering mammals is a slow, tedious, and expensive process.Murray, Joo (20)
Genetically modified animals
Canada: Brainwaving
As with other genetically modified organisms (GMOs), first genetic engineers must isolate the gene they wish to insert into the host organism. This can be taken from a
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
containing the gene or artificially synthesised. If the chosen gene or the donor organism's
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding gen ...
has been well studied it may already be accessible from a genetic library. The gene is then combined with other genetic elements, including a promoter and terminator region and usually a
selectable marker A selectable marker is a gene introduced into a cell, especially a bacterium or to cells in culture, that confers a trait suitable for artificial selection. They are a type of reporter gene used in laboratory microbiology, molecular biology, and gen ...
. A number of techniques are available for inserting the isolated gene into the host genome. With animals DNA is generally inserted into using
microinjection Microinjection is the use of a glass micropipette to inject a liquid substance at a microscopic or borderline macroscopic level. The target is often a living cell but may also include intercellular space. Microinjection is a simple mechanical pr ...
, where it can be injected through the cell's
nuclear envelope The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material. The nuclear envelope consists of two lipid bilayer membran ...
directly into the
nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...
, or through the use of
viral vectors Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved specialized molecula ...
. The first transgenic animals were produced by injecting viral DNA into embryos and then implanting the embryos in females. It is necessary to ensure that the inserted DNA is present in the
embryonic stem cells Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consis ...
. The embryo would develop and it would be hoped that some of the genetic material would be incorporated into the reproductive cells. Then researchers would have to wait until the animal reached breeding age and then offspring would be screened for presence of the gene in every cell, using
PCR PCR or pcr may refer to: Science * Phosphocreatine, a phosphorylated creatine molecule * Principal component regression, a statistical technique Medicine * Polymerase chain reaction ** COVID-19 testing, often performed using the polymerase chain r ...
, Southern hybridization, and
DNA sequencing DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. The ...
. New technologies are making genetic modifications easier and more precise.
Gene targeting Gene targeting (also, replacement strategy based on homologous recombination) is a genetic technique that uses homologous recombination to modify an endogenous gene. The method can be used to delete a gene, remove exons, add a gene and modify ind ...
techniques, which creates double-stranded breaks and takes advantage on the cells natural
homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may be ...
repair systems, have been developed to target insertion to exact
locations In geography, location or place are used to denote a region (point, line, or area) on Earth's surface or elsewhere. The term ''location'' generally implies a higher degree of certainty than ''place'', the latter often indicating an entity with an ...
.
Genome editing Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly inserts ...
uses artificially engineered
nuclease A nuclease (also archaically known as nucleodepolymerase or polynucleotidase) is an enzyme capable of cleaving the phosphodiester bonds between nucleotides of nucleic acids. Nucleases variously effect single and double stranded breaks in their ...
s that create breaks at specific points. There are four families of engineered nucleases:
meganuclease Meganucleases are endodeoxyribonucleases characterized by a large recognition site (double-stranded DNA sequences of 12 to 40 base pairs); as a result this site generally occurs only once in any given genome. For example, the 18-base pair sequence ...
s,
zinc finger nuclease Zinc-finger nucleases (ZFNs) are artificial restriction enzymes generated by fusing a zinc finger DNA-binding domain to a DNA-cleavage domain. Zinc finger domains can be engineered to target specific desired DNA sequences and this enables zin ...
s,
transcription activator-like effector nuclease Transcription activator-like effector nucleases (TALEN) are restriction enzymes that can be engineered to cut specific sequences of DNA. They are made by fusing a TAL effector DNA-binding domain to a DNA cleavage domain (a nuclease which cuts D ...
s (TALENs), and the Cas9-guideRNA system (adapted from
CRISPR CRISPR () (an acronym for clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bac ...
). TALEN and CRISPR are the two most commonly used and each has its own advantages. TALENs have greater target specificity, while CRISPR is easier to design and more efficient. The development of the CRISPR-Cas9 gene editing system has effectively halved the amount of time needed to develop genetically modified animals.


History

Humans have
domesticated Domestication is a sustained multi-generational relationship in which humans assume a significant degree of control over the reproduction and care of another group of organisms to secure a more predictable supply of resources from that group. A ...
animals since around 12,000 BCE, using
selective breeding Selective breeding (also called artificial selection) is the process by which humans use animal breeding and plant breeding to selectively develop particular phenotypic traits (characteristics) by choosing which typically animal or plant m ...
or artificial selection (as contrasted with
natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Charl ...
). The process of
selective breeding Selective breeding (also called artificial selection) is the process by which humans use animal breeding and plant breeding to selectively develop particular phenotypic traits (characteristics) by choosing which typically animal or plant m ...
, in which organisms with desired traits (and thus with the desired
genes In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
) are used to breed the next generation and organisms lacking the trait are not bred, is a precursor to the modern concept of genetic modification Various advancements in
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar working i ...
allowed humans to directly alter the DNA and therefore genes of organisms. In 1972,
Paul Berg Paul Berg (born June 30, 1926) is an American biochemist and professor emeritus at Stanford University. He was the recipient of the Nobel Prize in Chemistry in 1980, along with Walter Gilbert and Frederick Sanger. The award recognized their con ...
created the first
recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fou ...
molecule when he combined DNA from a monkey virus with that of the lambda virus. In 1974,
Rudolf Jaenisch Rudolf Jaenisch (born April 22, 1942) is a Professor of Biology at MIT and a founding member of the Whitehead Institute for Biomedical Research. He is a pioneer of transgenic science, in which an animal’s genetic makeup is altered. Jaenisch ...
created a transgenic mouse by introducing foreign DNA into its embryo, making it the world's first transgenic animal. However it took another eight years before transgenic mice were developed that passed the
transgene A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
to their offspring. Genetically modified mice were created in 1984 that carried cloned
oncogenes An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
, predisposing them to developing cancer. Mice with genes
knocked out A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, muay thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, a ...
(
knockout mouse A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are important ...
) were created in 1989. The first transgenic livestock were produced in 1985 and the first animal to synthesise transgenic proteins in their milk were mice, engineered to produce human tissue plasminogen activator in 1987. The first genetically modified animal to be commercialised was the
GloFish The GloFish is a patented and trademarked brand of genetically engineered fluorescent fish. They have been created from several different species of fish: zebrafish (''Danio rerio'') were the first GloFish available in pet stores, and recently te ...
, a
Zebra fish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...
with a fluorescent gene added that allows it to glow in the dark under ultraviolet light. It was released to the US market in 2003. The first genetically modified animal to be approved for food use was
AquAdvantage salmon AquAdvantage salmon is a genetically modified fish, genetically engineered (GE) fish, a GE Atlantic salmon developed by AquaBounty Technologies in 1989. The typical growth hormone-regulating gene in the Atlantic salmon was replaced with the grow ...
in 2015. The salmon were transformed with a
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
-regulating gene from a Pacific Chinook salmon and a promoter from an
ocean pout The ocean pout (''Zoarces americanus'') is an eelpout in the family Zoarcidae. It is found in the Northwest Atlantic Ocean, off the coast of New England and eastern Canada. The fish has antifreeze proteins in its blood, giving it the ability to ...
enabling it to grow year-round instead of only during spring and summer.


Mammals

GM mammals are created for research purposes, production of industrial or therapeutic products, agricultural uses or improving their health. There is also a market for creating genetically modified pets.Rudinko, Larisa (20). Guidance for industry. USA: Center for veterinary medicin
Link.
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Medicine

Mammals are the best models for human disease, making genetic engineered ones vital to the discovery and development of cures and treatments for many serious diseases. Knocking out genes responsible for human genetic disorders allows researchers to study the mechanism of the disease and to test possible cures. Genetically modified mice have been the most common mammals used in
biomedical research Medical research (or biomedical research), also known as experimental medicine, encompasses a wide array of research, extending from " basic research" (also called ''bench science'' or ''bench research''), – involving fundamental scienti ...
, as they are cheap and easy to manipulate. Pigs are also a good target, because they have a similar body size, anatomical features,
physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemica ...
, pathophysiological response, and diet. Nonhuman primates are the most similar model organisms to humans, but there is less public acceptance toward using them as research animals. In 2009, scientists announced that they had successfully transferred a gene into a
primate Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians (monkeys and apes, the latter including hum ...
species (
marmoset The marmosets (), also known as zaris or sagoin, are 22 New World monkey species of the genera '' Callithrix'', '' Cebuella'', '' Callibella'', and '' Mico''. All four genera are part of the biological family Callitrichidae. The term "marmose ...
s) and produced a stable line of breeding transgenic primates for the first time. Their first research target for these marmosets was
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
, but they were also considering
amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
and
Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...
. Human proteins expressed in mammals are more likely to be similar to their natural counterparts than those expressed in plants or microorganisms. Stable expression has been accomplished in sheep, pigs, rats, and other animals. In 2009, the first human biological drug produced from such an animal, a
goat The goat or domestic goat (''Capra hircus'') is a domesticated species of goat-antelope typically kept as livestock. It was domesticated from the wild goat (''C. aegagrus'') of Southwest Asia and Eastern Europe. The goat is a member of the a ...
., was approved. The drug,
ATryn ATryn is the brand name of the anticoagulant antithrombin manufactured by the Massachusetts-based U.S. company rEVO Biologics (formerly known as GTC Biotherapeutics). It is made from the milk of goats that have been genetically modified to produ ...
, is an
anticoagulant Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where the ...
which reduces the probability of
blood clot A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of ...
s during
surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
or childbirth was extracted from the goat's milk. Human alpha-1-antitrypsin is another protein that is used in treating humans with this deficiency. Another area is in creating pigs with greater capacity for human organ transplants (
xenotransplantation Xenotransplantation (''xenos-'' from the Greek meaning "foreign" or strange), or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenogra ...
). Pigs have been genetically modified so that their organs can no longer carry retroviruses or have modifications to reduce the chance of rejection. Pig lungs from genetically modified pigs are being considered for transplantation into humans. There is even potential to create chimeric pigs that can carry human organs.


Livestock

Livestock are modified with the intention of improving economically important traits such as growth-rate, quality of meat, milk composition, disease resistance and survival. Animals have been engineered to grow faster, be healthier and resist diseases. Modifications have also improved the wool production of sheep and udder health of cows. Goats have been genetically engineered to produce milk with strong spiderweb-like silk proteins. The goat gene sequence has been modified, using fresh umbilical cords taken from kids, in order to code for the human enzyme
lysozyme Lysozyme (EC 3.2.1.17, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside ...
. Researchers wanted to alter the milk produced by the goats, to contain lysozyme in order to fight off bacteria causing
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
in humans. Enviropig was a genetically enhanced line of Yorkshire pigs in Canada created with the capability of digesting plant
phosphorus Phosphorus is a chemical element with the symbol P and atomic number 15. Elemental phosphorus exists in two major forms, white phosphorus and red phosphorus, but because it is highly reactive, phosphorus is never found as a free element on Ea ...
more efficiently than conventional Yorkshire pigs.Guelph (2010)
Enviropig
. Canada:
The A
transgene A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
construct consisting of a promoter expressed in the
murine The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families excep ...
parotid gland The parotid gland is a major salivary gland in many animals. In humans, the two parotid glands are present on either side of the mouth and in front of both ears. They are the largest of the salivary glands. Each parotid is wrapped around the man ...
and the ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
''
phytase A phytase (''myo''-inositol hexakisphosphate phosphohydrolase) is any type of phosphatase enzyme that catalyzes the hydrolysis of phytic acid (myo-inositol hexakisphosphate) – an indigestible, organic form of phosphorus that is found in many pl ...
gene was introduced into the pig embryo by pronuclear
microinjection Microinjection is the use of a glass micropipette to inject a liquid substance at a microscopic or borderline macroscopic level. The target is often a living cell but may also include intercellular space. Microinjection is a simple mechanical pr ...
. This caused the pigs to produce the enzyme
phytase A phytase (''myo''-inositol hexakisphosphate phosphohydrolase) is any type of phosphatase enzyme that catalyzes the hydrolysis of phytic acid (myo-inositol hexakisphosphate) – an indigestible, organic form of phosphorus that is found in many pl ...
, which breaks down the indigestible phosphorus, in their saliva. As a result, they excrete 30 to 70% less phosphorus in manure depending upon the age and diet. The lower concentrations of phosphorus in surface runoff reduces
algal Algae (; singular alga ) is an informal term for a large and diverse group of photosynthesis, photosynthetic eukaryotic organisms. It is a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from u ...
growth, because phosphorus is the limiting nutrient for algae. Because algae consume large amounts of oxygen, excessive growth can result in dead zones for fish. Funding for the Enviropig program ended in April 2012, and as no new partners were found the pigs were killed. However, the genetic material will be stored at the Canadian Agricultural Genetics Repository Program. In 2006, a pig was engineered to produce
omega-3 fatty acid Omega−3 fatty acids, also called Omega-3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their chem ...
s through the expression of a
roundworm The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a broa ...
gene. In 1990, the world's first transgenic
bovine Bovines (subfamily Bovinae) comprise a diverse group of 10 genera of medium to large-sized ungulates, including cattle, bison, African buffalo, water buffalos, and the four-horned and spiral-horned antelopes. The evolutionary relationship betwe ...
, Herman the Bull, was developed. Herman was genetically engineered by micro-injected embryonic cells with the human gene coding for
lactoferrin Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, ...
. The
Dutch Parliament The States General of the Netherlands ( nl, Staten-Generaal ) is the supreme bicameral legislature of the Netherlands consisting of the Senate () and the House of Representatives (). Both chambers meet at the Binnenhof in The Hague. The Sta ...
changed the law in 1992 to allow Herman to reproduce. Eight calves were born in 1994 and all calves inherited the lactoferrin gene. With subsequent sirings, Herman fathered a total of 83 calves. Dutch law required Herman to be slaughtered at the conclusion of the
experiment An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a ...
. However the Dutch Agriculture Minister at the time, Jozias van Aartsen, granted him a reprieve provided he did not have more offspring after public and scientists rallied to his defence.Expatica News (2 April 2004). Herman the bull heads to greener pastures. Accessed on 3 January 2009 from http://www.expatica.com/nl/news/local_news/herman-the-bull-heads-to-greener-pastures--6273.html Together with
cloned Cloning is the process of producing individual organisms with identical or virtually identical DNA, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction. In the field of biotechnology, c ...
cows named Holly and Belle, he lived out his retirement at
Naturalis Naturalis Biodiversity Center ( nl, Nederlands Centrum voor Biodiversiteit Naturalis) is a national museum of natural history and a research center on biodiversity in Leiden, Netherlands. It was named the European Museum of the Year 2021. Al ...
, the National Museum of Natural History in Leiden. On 2 April 2004, Herman was euthanised by
veterinarian A veterinarian (vet), also known as a veterinary surgeon or veterinary physician, is a medical professional who practices veterinary medicine. They manage a wide range of health conditions and injuries in non-human animals. Along with this, vet ...
s from the
University of Utrecht Utrecht University (UU; nl, Universiteit Utrecht, formerly ''Rijksuniversiteit Utrecht'') is a public research university in Utrecht, Netherlands. Established , it is one of the oldest universities in the Netherlands. In 2018, it had an enrollm ...
because he suffered from
osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the ...
.Naturalis (2008). Herman the Bull stabled in Naturalis. Accessed 3 January 2009 from At the time of his death Herman was one of the oldest bulls in the Netherlands. Herman's hide has been preserved and mounted by
taxidermist Taxidermy is the art of preserving an animal's body via mounting (over an armature) or stuffing, for the purpose of display or study. Animals are often, but not always, portrayed in a lifelike state. The word ''taxidermy'' describes the proce ...
s and is permanently on display in Naturalis. They say that he represents the start of a new era in the way man deals with nature, an icon of scientific progress, and the subsequent public discussion of these issues. In October 2017, Chinese scientists announced they used CRISPR gene editing technology to create of a line of pigs with better body temperature regulation, resulting in about 24% less body fat than typical livestock. Researchers have developed GM dairy cattle to grow without horns (sometimes referred to as " polled") which can cause injuries to farmers and other animals. DNA was taken from the genome of
Red Angus The Red Angus is an international breed of beef cattle characterised by a reddish-brown coat colour. It derives from the Scottish Aberdeen Angus population and, apart from the coat colour, is identical to it. Red Angus are registered separatel ...
cattle, which is known to suppress horn growth, and inserted into cells taken from an elite
Holstein Holstein (; nds, label=Northern Low Saxon, Holsteen; da, Holsten; Latin and historical en, Holsatia, italic=yes) is the region between the rivers Elbe and Eider. It is the southern half of Schleswig-Holstein, the northernmost state of German ...
bull called "Randy". Each of the progeny will be a clone of Randy, but without his horns, and their offspring should also be hornless. In 2011, Chinese scientists generated
dairy cows Dairy cattle (also called dairy cows) are cattle bred for the ability to produce large quantities of milk, from which dairy products are made. Dairy cattle generally are of the species '' Bos taurus''. Historically, little distinction was ma ...
genetically engineered with genes from human beings to produce milk that would be the same as human breast milk. This could potentially benefit mothers who cannot produce breast milk but want their children to have breast milk rather than formula. The researchers claim these transgenic cows to be identical to regular cows. Two months later, scientists from
Argentina Argentina (), officially the Argentine Republic ( es, link=no, República Argentina), is a country in the southern half of South America. Argentina covers an area of , making it the second-largest country in South America after Brazil, th ...
presented Rosita, a transgenic cow incorporating two human genes, to produce milk with similar properties as human breast milk. In 2012, researchers from New Zealand also developed a genetically engineered cow that produced allergy-free milk. In 2016 Jayne Raper and a team announced the first trypanotolerant transgenic cow in the world. This team, spanning the International Livestock Research Institute,
Scotland's Rural College Scotland's Rural College (SRUC) is a public land based research institution focused on agriculture and life sciences. Its history stretches back to 1899 with the establishment of the West of Scotland Agricultural College and its current organis ...
, the
Roslin Institute The Roslin Institute is an animal sciences research institute at Easter Bush, Midlothian, Scotland, part of the University of Edinburgh, and is funded by the Biotechnology and Biological Sciences Research Council. It is best known for creating ...
's Centre for Tropical Livestock Genetics and Health, and the City University of New York, announced that a Kenyan Boran bull had been born and had already successfully had two children. Tumaini - named for the Swahili word for "hope" - carries a trypanolytic factor from a
baboon Baboons are primates comprising the genus ''Papio'', one of the 23 genera of Old World monkeys. There are six species of baboon: the hamadryas baboon, the Guinea baboon, the olive baboon, the yellow baboon, the Kinda baboon and the chacma b ...
via CRISPR/Cas9. p.276


Research

Scientists have genetically engineered several organisms, including some mammals, to include
green fluorescent protein The green fluorescent protein (GFP) is a protein that exhibits bright green fluorescence when exposed to light in the blue to ultraviolet range. The label ''GFP'' traditionally refers to the protein first isolated from the jellyfish '' Aequor ...
(GFP), for research purposes. GFP and other similar reporting genes allow easy visualisation and localisation of the products of the genetic modification. Fluorescent pigs have been bred to study human organ transplants, regenerating ocular
photoreceptor cell A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light (visible electromagnetic radiatio ...
s, and other topics. In 2011 green-fluorescent cats were created to find therapies for
HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...
and other diseases as
feline immunodeficiency virus Feline immunodeficiency virus (FIV) is a ''Lentivirus'' that affects cats worldwide, with 2.5% to 4.4% of felines being infected. FIV was first isolated in 1986, by Niels C Pedersen and Janet K. Yamamoto at the UC Davis School of Veterinar ...
(FIV) is related to HIV. Researchers from the University of Wyoming have developed a way to incorporate spiders' silk-spinning genes into goats, allowing the researchers to harvest the silk protein from the goats' milk for a variety of applications.


Conservation

Genetic modification of the
myxoma virus ''Myxoma virus'' is a poxvirus in the genus ''Leporipoxvirus''. The two broad geographic types of ''myxoma virus'' are Californian and South American. Californian ''myxoma virus'' is found on the West Coast of the United States, the Baja Peninsu ...
has been proposed to conserve European wild rabbits in the
Iberian peninsula The Iberian Peninsula (), ** * Aragonese and Occitan: ''Peninsula Iberica'' ** ** * french: Péninsule Ibérique * mwl, Península Eibérica * eu, Iberiar penintsula also known as Iberia, is a peninsula in southwestern Europe, defi ...
and to help regulate them in Australia. To protect the Iberian species from viral diseases, the myxoma virus was genetically modified to immunize the rabbits, while in Australia the same myxoma virus was genetically modified to lower fertility in the Australian rabbit population. There have also been suggestions that genetic engineering could be used to bring animals back from extinction. It involves changing the genome of a close living relative to resemble the extinct one and is currently being attempted with the
passenger pigeon The passenger pigeon or wild pigeon (''Ectopistes migratorius'') is an extinct species of pigeon that was endemic to North America. Its common name is derived from the French word ''passager'', meaning "passing by", due to the migratory habits ...
. Genes associated with the
woolly mammoth The woolly mammoth (''Mammuthus primigenius'') is an extinct species of mammoth that lived during the Pleistocene until its extinction in the Holocene epoch. It was one of the last in a line of mammoth species, beginning with '' Mammuthus subp ...
have been added to the genome of an African Elephant, although the lead researcher says he has no intention of using live elephants.


Humans

Gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
uses genetically modified viruses to deliver genes which can cure disease in humans. Although gene therapy is still relatively new, it has had some successes. It has been used to treat
genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
s such as
severe combined immunodeficiency Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in diffe ...
and
Leber's congenital amaurosis Leber congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life. It affects about 1 in 40,000 newborns. LCA was first described by Theodor Leber in the 19th century. It should not be ...
. Treatments are also being developed for a range of other currently incurable diseases, such as cystic fibrosis,
sickle cell anemia Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...
,
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
, cancer,
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
,
heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
, and
muscular dystrophy Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affe ...
. These treatments only affect
somatic cell A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells comp ...
s, which means that any changes would not be inheritable.
Germline In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They a ...
gene therapy results in any change being inheritable, which has raised concerns within the scientific community. In 2015, CRISPR was used to edit the DNA of non-viable human embryos. In November 2018,
He Jiankui He Jiankui (; ; born 1984) is a Chinese biophysics researcher who was an associate professor in the Department of Biology of the Southern University of Science and Technology (SUSTech) in Shenzhen, China. Earning his Ph.D. from Rice University ...
announced that he had edited the genomes of two human embryos, to attempt to disable the ''
CCR5 C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines. In humans, the ''CCR5'' gene that encodes the CCR5 pr ...
'' gene, which codes for a receptor that
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
uses to enter cells. He said that twin girls-
Lulu and Nana The He Jiankui affair is a scientific and bioethical controversy concerning the use of genome editing following its first use on humans by Chinese scientist He Jiankui, who edited the genomes of human embryos in 2018. He became widely known on ...
, had been born a few weeks earlier, and that they carried functional copies of CCR5 along with disabled CCR5 (
mosaicism Mosaicism or genetic mosaicism is a condition in multicellular organisms in which a single organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized ...
), and were still vulnerable to HIV. The work was widely condemned as unethical, dangerous, and premature.


Fish

Genetically modified fish are used for scientific research, as pets, and as a food source.
Aquaculture Aquaculture (less commonly spelled aquiculture), also known as aquafarming, is the controlled cultivation ("farming") of aquatic organisms such as fish, crustaceans, mollusks, algae and other organisms of value such as aquatic plants (e.g. lot ...
is a growing industry, currently providing over half of the consumed fish worldwide. Through genetic engineering, it is possible to increase growth rates, reduce food intake, remove allergenic properties, increase cold tolerance, and provide disease resistance.


Detecting pollution

Fish can also be used to detect aquatic pollution or function as bioreactors. Several groups have been developing
zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...
to detect pollution by attaching fluorescent proteins to genes activated by the presence of pollutants. The fish will then glow and can be used as environmental sensors.


Pets

The
GloFish The GloFish is a patented and trademarked brand of genetically engineered fluorescent fish. They have been created from several different species of fish: zebrafish (''Danio rerio'') were the first GloFish available in pet stores, and recently te ...
is a brand of genetically modified fluorescent
zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...
with bright red, green, and orange fluorescent color. It was originally developed by one of the groups to detect pollution, but is now part of the ornamental fish trade, becoming the first genetically modified animal to become publicly available as a pet when it was introduced for sale in 2003.


Research

GM fish are widely used in basic research in genetics and development. Two species of fish- zebrafish and medaka, are most commonly modified, because they have optically clear chorions (membranes in the egg), rapidly develop, and the 1-cell embryo is easy to see and microinject with transgenic DNA. Zebrafish are model organisms for developmental processes,
regeneration Regeneration may refer to: Science and technology * Regeneration (biology), the ability to recreate lost or damaged cells, tissues, organs and limbs * Regeneration (ecology), the ability of ecosystems to regenerate biomass, using photosynthesis ...
, genetics, behaviour, disease mechanisms, and toxicity testing. Their transparency allows researchers to observe developmental stages, intestinal functions, and tumour growth. The generation of transgenic protocols (whole organism, cell or tissue specific, tagged with reporter genes) has increased the level of information gained by studying these fish.


Growth

GM fish have been developed with promoters driving an over-production of "all fish"
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
for use in the
aquaculture Aquaculture (less commonly spelled aquiculture), also known as aquafarming, is the controlled cultivation ("farming") of aquatic organisms such as fish, crustaceans, mollusks, algae and other organisms of value such as aquatic plants (e.g. lot ...
industry, to increase the speed of development and potentially reduce fishing pressure on wild stocks. This has resulted in dramatic growth enhancement in several species, including
salmon Salmon () is the common name for several commercially important species of euryhaline ray-finned fish from the family Salmonidae, which are native to tributaries of the North Atlantic (genus ''Salmo'') and North Pacific (genus ''Oncorhynchus' ...
,
trout Trout are species of freshwater fish belonging to the genera ''Oncorhynchus'', ''Salmo'' and ''Salvelinus'', all of the subfamily Salmoninae of the family Salmonidae. The word ''trout'' is also used as part of the name of some non-salmonid ...
, and
tilapia Tilapia ( ) is the common name for nearly a hundred species of cichlid fish from the coelotilapine, coptodonine, heterotilapine, oreochromine, pelmatolapiine, and tilapiine tribes (formerly all were "Tilapiini"), with the economically most ...
. AquaBounty Technologies have produced a salmon that can mature in half the time as wild salmon. The fish is an Atlantic salmon with a
Chinook salmon The Chinook salmon (''Oncorhynchus tshawytscha'') is the largest and most valuable species of Pacific salmon in North America, as well as the largest in the genus ''Oncorhynchus''. Its common name is derived from the Chinookan peoples. Other ve ...
(''Oncorhynchus tshawytscha'') gene inserted. This allows the fish to produce growth hormones all year round compared to the wild-type fish that produces the hormone for only part of the year. The fish also has a second gene inserted from the eel-like
ocean pout The ocean pout (''Zoarces americanus'') is an eelpout in the family Zoarcidae. It is found in the Northwest Atlantic Ocean, off the coast of New England and eastern Canada. The fish has antifreeze proteins in its blood, giving it the ability to ...
that acts like an "on" switch for the hormone. Pout also have
antifreeze protein Antifreeze proteins (AFPs) or ice structuring proteins refer to a class of polypeptides produced by certain animals, plants, fungi and bacteria that permit their survival in temperatures below the freezing point of water. AFPs bind to small ...
s in their blood, which allow the GM salmon to survive near-freezing waters and continue their development. A wild-type salmon takes 24 to 30 months to reach market size (4–6 kg), whereas the producers of the GM salmon say that it requires only 18 months for the GM fish to reach that size.Environmental Assessment for AquAdvantage Salmon
/ref> In November 2015, the FDA of the USA approved the
AquAdvantage salmon AquAdvantage salmon is a genetically modified fish, genetically engineered (GE) fish, a GE Atlantic salmon developed by AquaBounty Technologies in 1989. The typical growth hormone-regulating gene in the Atlantic salmon was replaced with the grow ...
for commercial production, sale, and consumption, the first non-plant GMO food to be commercialized. AquaBounty says that to prevent the genetically modified fish from inadvertently breeding with wild salmon, all of the fish will be female and reproductively sterile, although a small percentage of the females may remain fertile. Some opponents of the GM salmon have dubbed it the "Frankenfish".


Insects


Research

In biological research, transgenic fruit flies (''
Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly" or "pomace fly". Starting with Ch ...
'') are
model organism A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the working ...
s used to study the effects of genetic changes on development. Fruit flies are often preferred over other animals due to their short life cycle and low maintenance requirements. It also has a relatively simple genome compared to many
vertebrates Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...
, with typically only one copy of each gene, making phenotypic analysis easy. ''Drosophila'' have been used to study genetics and inheritance, embryonic development, learning, behavior, and aging.
Transposons A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Trans ...
(particularly P elements) are well developed in ''Drosophila'' and provided an early method to add transgenes to their genome, although this has been taken over by more modern gene-editing techniques.


Population control

Due to their significance to human health, scientists are looking at ways to control mosquitoes through genetic engineering. Malaria-resistant mosquitoes have been developed in the laboratory. by inserting a gene that reduces the development of the malaria parasite and then use
homing endonuclease The homing endonucleases are a collection of endonucleases encoded either as freestanding genes within introns, as fusions with host proteins, or as self-splicing inteins. They catalyze the hydrolysis of genomic DNA within the cells that synthes ...
s to rapidly spread that gene throughout the male population (known as a
gene drive A gene drive is a natural process and technology of genetic engineering that propagates a particular suite of genes throughout a population by altering the probability that a specific allele will be transmitted to offspring (instead of the Mende ...
). This has been taken further by swapping it for a lethal gene. In trials the populations of ''
Aedes aegypti ''Aedes aegypti'', the yellow fever mosquito, is a mosquito that can spread dengue fever, chikungunya, Zika fever, Mayaro and yellow fever viruses, and other disease agents. The mosquito can be recognized by black and white markings on its legs ...
'' mosquitoes, the single most important carrier of dengue fever and Zika virus, were reduced by between 80% and by 90%. Another approach is to use the
sterile insect technique The sterile insect technique (SIT) is a method of biological insect control, whereby overwhelming numbers of sterile insects are released into the wild. The released insects are preferably male, as this is more cost-effective and the females ...
, whereby males genetically engineered to be sterile out compete viable males, to reduce population numbers. Other insect pests that make attractive targets are
moth Moths are a paraphyletic group of insects that includes all members of the order Lepidoptera that are not butterflies, with moths making up the vast majority of the order. There are thought to be approximately 160,000 species of moth, many of w ...
s.
Diamondback moth The diamondback moth (''Plutella xylostella''), sometimes called the cabbage moth, is a moth species of the family Plutellidae and genus '' Plutella''. The small, grayish-brown moth sometimes has a cream-colored band that forms a diamond along ...
s cause US$4 to $5 billion of damage a year worldwide. The approach is similar to the mosquitoes, where males transformed with a gene that prevents females from reaching maturity will be released. They underwent field trials in 2017. Genetically modified moths have previously been released in field trials. A strain of pink bollworm that were sterilised with radiation were genetically engineered to express a
red fluorescent protein Red fluorescent protein (RFP) is a fluorophore that fluoresces red-orange when excited. Several variants have been developed using directed mutagenesis. The original was isolated from Discosoma, and named DsRed. Others are now available that flu ...
making it easier for researchers to monitor them.


Industry

Silkworm, the larvae stage of ''
Bombyx mori The domestic silk moth (''Bombyx mori''), is an insect from the moth family Bombycidae. It is the closest relative of ''Bombyx mandarina'', the wild silk moth. The silkworm is the larva or caterpillar of a silk moth. It is an economically imp ...
,'' is an economically important insect in
sericulture Sericulture, or silk farming, is the cultivation of silkworms to produce silk. Although there are several commercial species of silkworms, ''Bombyx mori'' (the caterpillar of the domestic silkmoth) is the most widely used and intensively studi ...
. Scientists are developing strategies to enhance silk quality and quantity. There is also potential to use the silk producing machinery to make other valuable proteins. Proteins expressed by silkworms include;
human serum albumin Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver. It is soluble in water, and it is monomeric. Albumin ...
, human collagen α-chain, mouse monoclonal antibody and N-glycanase. Silkworms have been created that produce
spider silk Spider silk is a protein fibre spun by spiders. Spiders use their silk to make webs or other structures, which function as sticky nets to catch other animals, or as nests or cocoons to protect their offspring, or to wrap up prey. They can ...
, a stronger but extremely difficult to harvest silk, and even novel silks.


Birds

Attempts to produce genetically modified birds began before 1980. Chickens have been genetically modified for a variety of purposes. This includes studying embryo development, preventing the transmission of bird flu and providing evolutionary insights using
reverse engineering Reverse engineering (also known as backwards engineering or back engineering) is a process or method through which one attempts to understand through deductive reasoning how a previously made device, process, system, or piece of software accompli ...
to recreate dinosaur-like phenotypes. A GM chicken that produces the drug Kanuma, an enzyme that treats a rare condition, in its egg passed regulatory approval in 2015.


Disease control

One potential use of GM birds could be to reduce the spread of avian disease. Researchers at
Roslin Institute The Roslin Institute is an animal sciences research institute at Easter Bush, Midlothian, Scotland, part of the University of Edinburgh, and is funded by the Biotechnology and Biological Sciences Research Council. It is best known for creating ...
have produced a strain of GM chickens (''Gallus gallus domesticus'') that does not transmit
avian flu Avian influenza, known informally as avian flu or bird flu, is a variety of influenza caused by viruses adapted to birds.RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
molecule that prevents the virus reproduction by mimicking the region of the flu virus genome that controls replication. It is referred to as a "decoy" because it diverts the flu virus enzyme, the
polymerase A polymerase is an enzyme ( EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using bas ...
, from functions that are required for virus replication.


Evolutionary insights

A team of geneticists led by
University of Montana The University of Montana (UM) is a public research university in Missoula, Montana. UM is a flagship institution of the Montana University System and its second largest campus. UM reported 10,962 undergraduate and graduate students in the fa ...
paleontologist Jack Horner is seeking to modify a chicken to express several features present in ancestral
maniraptora Maniraptora is a clade of coelurosaurian dinosaurs which includes the birds and the non-avian dinosaurs that were more closely related to them than to ''Ornithomimus velox''. It contains the major subgroups Avialae, Deinonychosauria, Oviraptor ...
ns but absent in modern birds, such as teeth and a long tail, creating what has been dubbed a 'chickenosaurus'. Parallel projects have produced chicken embryos expressing dinosaur-like skull, leg, and foot anatomy.


Amphibians

The first experiments that successfully developed
transgenic A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
amphibians into embryos began in the 1980s with Xenopus laevis. Later, germline transgenic axolotls in
Ambystoma mexicanum The axolotl (; from nci, āxōlōtl ), ''Ambystoma mexicanum'', is a paedomorphic salamander closely related to the tiger salamander. Axolotls are unusual among amphibians in that they reach adulthood without undergoing metamorphosis. Instea ...
were produced in 2006 using a technique called I-SceI-mediated transgenesis which utilizes the I-SceI endonuclease enzyme that can break DNA at specific sites and allow for foreign DNA to be inserted into the genome. Both Xenopus laevis and Ambystoma mexicanum are model organisms used to study
regeneration Regeneration may refer to: Science and technology * Regeneration (biology), the ability to recreate lost or damaged cells, tissues, organs and limbs * Regeneration (ecology), the ability of ecosystems to regenerate biomass, using photosynthesis ...
. In addition, transgenic lines have been produced in other salamanders including the Japanese newt Pyrrhogaster and Pleurodeles watl. Genetically modified frogs, in particular ''
Xenopus laevis The African clawed frog (''Xenopus laevis'', also known as the xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the three short claws ...
'' and ''
Xenopus tropicalis The western clawed frog (''Xenopus tropicalis'') is a species of frog in the family Pipidae, also known as tropical clawed frog. It is the only species in the genus ''Xenopus'' to have a diploid genome. Its genome has been sequenced, making it a ...
'', are used in development biology. GM frogs can also be used as pollution sensors, especially for endocrine disrupting chemicals. There are proposals to use genetic engineering to control cane toads in Australia. Many lines of transgenic X. laevis are used to study immunology to address how bacteria and viruses cause infectious disease at the University of Rochester Medical Center’s X. laevis Research Resource for Immunobiology (XLRRI). Amphibians can also be used to study and validate regenerative
signaling pathways Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular ...
such as the
Wnt pathway The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling ...
. The wound-healing abilities of amphibians have many practical applications and can potentially provide a foundation for scar-free repair in human plastic surgery, such as treating the skin of burn patients. Amphibians like X. laevis are suitable for experimental
embryology Embryology (from Greek ἔμβρυον, ''embryon'', "the unborn, embryo"; and -λογία, ''-logia'') is the branch of animal biology that studies the prenatal development of gametes (sex cells), fertilization, and development of embryos an ...
because they have large embryos that can be easily manipulated and observed during development. In experiments with axolotls, mutants with white pigmented skin are often used because their semi-transparent skin provides an efficient visualization and tracking method for fluorescently tagged proteins like GFP. Amphibians are not always ideal when it comes to the resources required to produce genetically modified animals; along with the one to two-year generation time, Xenopus laevis can be considered less than ideal for transgenic experiments because of its pseudotetraploid genome. Due to the same genes appearing in the genome multiple times, the chance of
mutagenesis Mutagenesis () is a process by which the genetic information of an organism is changed by the production of a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using lab ...
experiments working is lower. Current methods of freezing and thawing axolotl sperm render them nonfunctional, meaning transgenic lines must be maintained in a facility and this can get quite costly. Producing transgenic axolotls has many challenges due to their large genome size. Current methods of generating transgenic axolotls are limited to random integration of the transgene cassette into the genome, which can lead to uneven expression or silencing. Gene duplicates also complicate efforts to generate efficient gene knockouts. Despite the costs, axolotls have unique regenerative abilities and ultimately provide useful information in understanding tissue regeneration because they can regenerate their limbs, spinal cord, skin, heart, lungs, and other organs. Naturally occurring mutant axolotls like the white strain that are often used in research have a transcriptional mutation at the Edn3 gene locus. Unlike other model organisms, the first fluorescently labeled cells in axolotls were differentiated muscle cells instead of embryos. In these initial experiments in the early 2000s, scientists were able to visualize muscle cell regeneration in the axolotl tail using a microinjecting technique, but cells could not be traced for the entire course of regeneration due to too harsh conditions that caused early cell death in labeled cells. Though the process of producing transgenic axolotls was a challenge, scientists were able to label cells for longer durations using a plasmid transfection technique, which involves injecting DNA into cells using an electrical pulse in a process called
electroporation Electroporation, or electropermeabilization, is a microbiology technique in which an electrical field is applied to cells in order to increase the permeability of the cell membrane, allowing chemicals, drugs, electrode arrays or DNA to be introdu ...
. Transfecting axolotl cells is thought to be more difficult because of the composition of the
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide struct ...
(ECM). This technique allows spinal cord cells to be labeled and is very important in studying limb regeneration in many other cells; it has been used to study the role of the immune system in regeneration. Using
gene knockout A gene knockout (abbreviation: KO) is a genetic technique in which one of an organism's genes is made inoperative ("knocked out" of the organism). However, KO can also refer to the gene that is knocked out or the organism that carries the gene kno ...
approaches, scientists can target specific regions of DNA using techniques like CRISPR/Cas9 to understand the function of certain genes based on the absence of the gene of interest. For example, gene knockouts of the Sox2 gene confirm this region’s role in neural stem cell amplification in the axolotl. The technology to do more complex conditional gene knockouts, or conditional knockouts that give the scientist spatiotemporal control of the gene is not yet suitable for axolotls. However, research in this field continues to develop and is made easier by recent sequencing of the genome and resources created for scientists, including data portals that contain axolotl genome and transcriptome reference assemblies to identify
orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spe ...
.


Nematodes

The
nematode The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant- parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a bro ...
''
Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
'' is one of the major model organisms for researching
molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
.
RNA interference RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by o ...
(RNAi) was discovered in ''C elegans'' and could be induced by simply feeding them bacteria modified to express double stranded RNA. It is also relatively easy to produce stable transgenic nematodes and this along with RNAi are the major tools used in studying their genes. The most common use of transgenic nematodes has been studying gene expression and localisation by attaching reporter genes. Transgenes can also be combined with RNAi to rescue phenotypes, altered to study gene function, imaged in real time as the cells develop or used to control expression for different tissues or developmental stages. Transgenic nematodes have been used to study viruses, toxicology, and diseases and to detect environmental pollutants.


Other

Systems have been developed to create transgenic organisms in a wide variety of other animals. The gene responsible for
albinism Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and pink or blue eyes. Individuals with the condition are referred to as albino. Varied use and interpretation of the term ...
in
sea cucumber Sea cucumbers are echinoderms from the class Holothuroidea (). They are marine animals with a leathery skin and an elongated body containing a single, branched gonad. Sea cucumbers are found on the sea floor worldwide. The number of holothuria ...
s has been found, and used to engineer white sea cucumbers, a rare delicacy. The technology also opens the way to investigate the genes responsible for some of the cucumbers more unusual traits, including
hibernating Hibernation is a state of minimal activity and metabolic depression undergone by some animal species. Hibernation is a seasonal heterothermy characterized by low body-temperature, slow breathing and heart-rate, and low metabolic rate. It most ...
in summer, eviscerating their intestines, and dissolving their bodies upon death.
Flatworm The flatworms, flat worms, Platyhelminthes, or platyhelminths (from the Greek πλατύ, ''platy'', meaning "flat" and ἕλμινς (root: ἑλμινθ-), ''helminth-'', meaning "worm") are a phylum of relatively simple bilaterian, unsegment ...
s have the ability to regenerate themselves from a single cell. * Until 2017 there was no effective way to transform them, which hampered research. By using microinjection and radiation, scientists have now created the first genetically modified flatworms. The
bristle worm Polychaeta () is a paraphyletic class of generally marine annelid worms, commonly called bristle worms or polychaetes (). Each body segment has a pair of fleshy protrusions called parapodia that bear many bristles, called chaetae, which are ...
, a marine
annelid The annelids (Annelida , from Latin ', "little ring"), also known as the segmented worms, are a large phylum, with over 22,000 extant species including ragworms, earthworms, and leeches. The species exist in and have adapted to various ecolo ...
, has been modified. It is of interest due to its reproductive cycle being synchronized with lunar phases, regeneration capacity and slow evolution rate.
Cnidaria Cnidaria () is a phylum under kingdom Animalia containing over 11,000 species of aquatic animals found both in freshwater and marine environments, predominantly the latter. Their distinguishing feature is cnidocytes, specialized cells that th ...
such as '' Hydra'' and the sea anemone ''
Nematostella vectensis The starlet sea anemone (''Nematostella vectensis'') is a species of small sea anemone in the family Edwardsiidae native to the east coast of the United States, with introduced populations along the coast of southeast England and the west coast ...
'' are attractive model organisms to study the
evolution Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
of
immunity Immunity may refer to: Medicine * Immunity (medical), resistance of an organism to infection or disease * ''Immunity'' (journal), a scientific journal published by Cell Press Biology * Immune system Engineering * Radiofrequence immunity desc ...
and certain developmental processes. Other organisms that have been genetically modified include
snail A snail is, in loose terms, a shelled gastropod. The name is most often applied to land snails, terrestrial pulmonate gastropod molluscs. However, the common name ''snail'' is also used for most of the members of the molluscan class Gastrop ...
s,
gecko Geckos are small, mostly carnivorous lizards that have a wide distribution, found on every continent except Antarctica. Belonging to the infraorder Gekkota, geckos are found in warm climates throughout the world. They range from . Geckos are ...
s,
turtle Turtles are an order of reptiles known as Testudines, characterized by a special shell developed mainly from their ribs. Modern turtles are divided into two major groups, the Pleurodira (side necked turtles) and Cryptodira (hidden necked t ...
s,
crayfish Crayfish are freshwater crustaceans belonging to the clade Astacidea, which also contains lobsters. In some locations, they are also known as crawfish, craydids, crawdaddies, crawdads, freshwater lobsters, mountain lobsters, rock lobsters, mu ...
,
oyster Oyster is the common name for a number of different families of salt-water bivalve molluscs that live in marine or brackish habitats. In some species, the valves are highly calcified, and many are somewhat irregular in shape. Many, but not a ...
s,
shrimp Shrimp are crustaceans (a form of shellfish) with elongated bodies and a primarily swimming mode of locomotion – most commonly Caridea and Dendrobranchiata of the decapod order, although some crustaceans outside of this order are referre ...
, clams,
abalone Abalone ( or ; via Spanish , from Rumsen ''aulón'') is a common name for any of a group of small to very large marine gastropod molluscs in the family Haliotidae. Other common names are ear shells, sea ears, and, rarely, muttonfish or m ...
, and
sponge Sponges, the members of the phylum Porifera (; meaning 'pore bearer'), are a basal animal clade as a sister of the diploblasts. They are multicellular organisms that have bodies full of pores and channels allowing water to circulate through ...
s.


References

{{genetic engineering Genetic engineering Genetically modified organisms