Genetically modified mammals are mammals that have been

genetically engineered 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 t ...

. They are an important category of genetically modified organisms. The majority of research involving genetically modified mammals involves mice with attempts to produce knockout animals in other mammalian species limited by the inability to derive and stably culture

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 consist ...

Usage

The majority of genetically modified mammals are used in research to investigate changes in

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...

when specific genes are altered. This can be used to discover the function of an unknown gene, any genetic interactions that occur or where the gene is expressed. Genetic modification can also produce mammals that are susceptible to certain compounds or stresses for testing in biomedical research. Some genetically modified mammals are used as models of human diseases and potential treatments and cures can first be tested on them. Other mammals have been engineered with the aim of potentially increasing their use to medicine and industry. These possibilities include pigs expressing human antigens aiming to increasing the success of

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 xenograft ...

to lactating mammals expressing useful proteins in their milk.

Mice

Genetically modified mice are often used to study cellular and tissue-specific responses to disease (cf

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 importa ...

). This is possible since mice can be created with the same

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral repl ...

s that occur in human

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, the production of the human disease in these mice then allows treatments to be tested. The

oncomouse The OncoMouse or Harvard mouse is a type of laboratory mouse (''Mus musculus'') that has been genetically modified using modifications designed by Philip Leder and Timothy A Stewart of Harvard University to carry a specific gene called an activ ...

is a type of

laboratory mouse The laboratory mouse or lab mouse is a small mammal of the order Rodentia which is bred and used for scientific research or feeders for certain pets. Laboratory mice are usually of the species '' Mus musculus''. They are the most commonly ...

that has 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 ...

developed by

Philip Leder Philip Leder (November 19, 1934 – February 2, 2020) was an American geneticist. Early life and education Leder was born in Washington, D.C. and studied at Harvard University, graduating in 1956. In 1960, he graduated from Harvard Medical Sc ...

and Timothy A. Stewart of

Harvard University Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of high ...

to carry a specific

gene 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 b ...

called an activated

oncogene 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.

Metabolic supermice PEPCK-Cmus mice are genetically modified mice (''Mus musculus'') which as a result of their modification have up to 100 times the concentration of the PEPCK-C enzyme in their muscles, compared to ordinary mice. They were created by a team of Ame ...

are the creation of a team of American scientists led by Richard Hanson, professor of

biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...

at Case Western Reserve University at Cleveland, Ohio. The aim of the research was to gain a greater understanding of the PEPCK-C enzyme, which is present mainly in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

and

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

Rats

knockout rat A knockout rat is a genetically engineered rat with a single gene turned off through a targeted mutation (gene trapping) used for academic and pharmaceutical research. Knockout rats can mimic human diseases and are important tools for studying ...

is a rat with a single gene disruption used for academic and pharmaceutical research.

Goats

BioSteel is a

trademark A trademark (also written trade mark or trade-mark) is a type of intellectual property consisting of a recognizable sign, design, or expression that identifies products or services from a particular source and distinguishes them from othe ...

name for a high-strength based fiber material made of the recombinant

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 ...

-like protein extracted from the milk of

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 ...

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 ...

s, made by Nexia Biotechnologies. Prior to its bankruptcy, the company successfully generated distinct lines of goats that produced recombinant versions of either the MaSpI or MaSpII dragline silk proteins, respectively, in their milk.

Pigs

The

enviropig Genetically modified animals are animals that have been genetically modified 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 ...

is the trademark for a

line of Yorkshire pigs with the capability to digest plant phosphorus more efficiently than ordinary unmodified pigs that was developed at the

University of Guelph , mottoeng = "to learn the reasons of realities" , established = May 8, 1964 ()As constituents: OAC: (1874) Macdonald Institute: (1903) OVC: (1922) , type = Public university , chancellor ...

. Enviropigs 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 p ...

in the salivary glands that is secreted in the saliva. In 2006 the scientists from

National Taiwan University National Taiwan University (NTU; ) is a public research university in Taipei, Taiwan. The university was founded in 1928 during Japanese rule as the seventh of the Imperial Universities. It was named Taihoku Imperial University and served d ...

's Department of Animal Science and Technology managed to breed three green-glowing pigs using green fluorescent protein. Fluorescent pigs can be used to study human organ transplants,Staff (8 January 2008
Fluorescent Chinese pig passes on trait to offspring
AFP, Retrieved 31 August 2012 regenerating ocular photoreceptor cells,

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...

al cells in the brain,

regenerative medicine Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". This field holds the promise of engineering damaged tissues and organs by st ...

via stem cells,

tissue engineering Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering, materials methods, and suitable biochemical and physicochemical factors to restore, maintain, improve, or replace different types of biolog ...

, and other diseases. In 2015, researchers at the Beijing Genomics Institute used

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 DNA ...

s to create a miniature version of the Bama breed of pigs, and offered them for sale to consumers. In 2017 scientists at 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 creat ...

of the University of Edinburgh, in collaboration with

Genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial nom ...

, reported they had bred pigs with a modified

CD163 CD163 (Cluster of Differentiation 163) is a protein that in humans is encoded by the CD163 gene. CD163 is the high affinity scavenger receptor for the hemoglobin-haptoglobin complex and in the absence of haptoglobin - with lower affinity - for hem ...

gene. These pigs were completely resistant to Porcine Reproductive and Respiratory Syndrome, a disease that causes major losses in the world-wide pig industry.

Cattle

In 1991,

Herman the Bull Genetically modified animals are animals that have been genetically modified 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 ...

was the first genetically modified or 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 ...

in the world.Naturalis (2008). Herman the Bull stabled in Naturalis. Accessed on 3 January 2009 from www.naturalis.nl/naturalis.en/naturalis.en/i000968.html. The announcement of Herman's creation generated considerable controversy.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 In 2016 Jayne Raper and her team announced the first trypanotolerant transgenic cow in the world. This team, spanning the

International Livestock Research Institute The International Livestock Research Institute or ILRI is an international agricultural research institute within the CGIAR – formerly the Consultative Group for International Agricultural Research. It was established in 1994 by merger of t ...

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

's Centre for Tropical Livestock Genetics and Health, and the City University of New York, announced that a

Kenyan Boran Boran cattle are a popular Zebu beef breed in eastern Africa. Through DNA sampling, Hanotte et al. have analyzed the genetic make-up of the Boran and it consists of the following genetic proportions—64% ''Bos indicus'', 24% European ''Bos tau ...

bull had been born and had already successfully had two children. Tumaini – named for the Swahili word for "hope" – had been given a

trypanolytic factor A trypanotolerant organism is one which is relatively less affected by trypanosome infestation. By host In humans In livestock Some breeds are known for their trypanotolerance. This is especially important in Africa where a few particular tryp ...

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 ...

via CRISPR/Cas9. p.276

Dogs

Ruppy Ruppy (short for Ruby Puppy) is the world's first transgenic dog. A cloned beagle, Ruppy and four other beagles produce a fluorescent protein that glows red upon excitation with ultraviolet light. Ruppy was created in 2009 by a group of scienti ...

(short for Ruby Puppy) was in 2009 the world's first

dog. A cloned

beagle The beagle is a breed of small scent hound, similar in appearance to the much larger foxhound. The beagle was developed primarily for hunting hare, known as beagling. Possessing a great sense of smell and superior tracking instincts, th ...

, Ruppy and four other beagles produced a fluorescent protein that glowed red upon excitation with ultraviolet light. It was hoped to use this procedure to investigate the effect of the hormone

oestrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

on fertility. A team in China reported in 2015 that they had genetically engineered

s to have twice the normal muscle mass, inserting a natural myostatin gene mutation taken from

whippet The Whippet is a dog breed of medium size. It is a sighthound breed that originated in England, descended from the Greyhound. Whippets today still strongly resemble a smaller Greyhound. Part of the hound group, Whippets have relatively few ...

Primates

In 2009 scientists in Japan 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 ...

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 "marmoset" ...

s) and produced a stable line of breeding transgenic primates for the first time. It was hoped that this would aid research into human diseases that cannot be studied in mice, for example

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 uns ...

, strokes, Alzheimer's disease and

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...

Cats

In 2011 a Japanese-American Team created genetically modified green-fluorescent

cat The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of ...

s in order to study

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 ...

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 Veterinary M ...

(FIV) is related to HIV.Staff (3 April 2012
Biology of HIV
National Institute of Allergy and Infectious Diseases, Retrieved 31 August 2012

References

{{DEFAULTSORT:Genetically Modified Mammal Genetically modified organisms