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The zebrafish (''Danio rerio'') is a
freshwater fish Freshwater fish are those that spend some or all of their lives in fresh water, such as rivers and lakes, with a salinity of less than 1.05%. These environments differ from marine conditions in many ways, especially the difference in levels of s ...
belonging to the minnow family (
Cyprinidae Cyprinidae is a family of freshwater fish commonly called the carp or minnow family. It includes the carps, the true minnows, and relatives like the barbs and barbels. Cyprinidae is the largest and most diverse fish family and the largest verte ...
) of the
order Order, ORDER or Orders may refer to: * Categorization, the process in which ideas and objects are recognized, differentiated, and understood * Heterarchy, a system of organization wherein the elements have the potential to be ranked a number of d ...
Cypriniformes Cypriniformes is an order of ray-finned fish, including the carps, minnows, loaches, and relatives. Cypriniformes is an Order within the Superorder Ostariophysi consisting of "Carp-like" Ostariophysins. This order contains 11-12 families, ...
. Native to South Asia, it is a popular
aquarium fish Lists of aquarium life include lists of fish, amphibians, invertebrates and plants in freshwater, brackish and marine aquariums. In fishkeeping, suitable species of aquarium fish, plants and other organisms vary with the size, water chemistry and ...
, frequently sold under the trade name zebra danio (and thus often called a " tropical fish" although both tropical and
subtropical The subtropical zones or subtropics are geographical zone, geographical and Köppen climate classification, climate zones to the Northern Hemisphere, north and Southern Hemisphere, south of the tropics. Geographically part of the Geographical z ...
). It is also found in private ponds. The zebrafish is an important and widely used vertebrate
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 workin ...
in scientific research, for example in drug development, in particular
pre-clinical development In drug development, preclinical development, also termed preclinical studies or nonclinical studies, is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and drug ...
. It is also notable for its regenerative abilities, and has been
modified Modified may refer to: * ''Modified'' (album), the second full-length album by Save Ferris * Modified racing, or "Modifieds", an American automobile racing genre See also * Modification (disambiguation) * Modifier (disambiguation) Modifier may ...
by researchers to produce many
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 ...
strains.


Taxonomy

The zebrafish is a
derived Derive may refer to: * Derive (computer algebra system), a commercial system made by Texas Instruments * ''Dérive'' (magazine), an Austrian science magazine on urbanism *Dérive, a psychogeographical concept See also * *Derivation (disambiguatio ...
member of the genus ''
Brachydanio The danionins are a group of small, minnow-type fish belonging to the family Cyprinidae. Members of this group are mostly in the genera ''Danio'', ''Devario'', and ''Rasbora''._They_are_primarily_native_to_the_ s_...''._They_are_primarily_native ...
'', of the family
Cyprinidae Cyprinidae is a family of freshwater fish commonly called the carp or minnow family. It includes the carps, the true minnows, and relatives like the barbs and barbels. Cyprinidae is the largest and most diverse fish family and the largest verte ...
. It has a sister-group relationship with ''
Danio aesculapii The panther danio (''Danio aesculapii'') is a species of danio endemic to Myanmar Myanmar, ; UK pronunciations: US pronunciations incl. . Note: Wikipedia's IPA conventions require indicating /r/ even in British English although only som ...
''. Zebrafish are also closely related to the genus ''
Devario ''Devario'' is a genus of fish in the family Cyprinidae native to the rivers and streams of South and Southeast Asia. These fishes have short barbels and many species having vertical or horizontal stripes. These species consume various small, aqu ...
'', as demonstrated by a
phylogenetic tree A phylogenetic tree (also phylogeny or evolutionary tree Felsenstein J. (2004). ''Inferring Phylogenies'' Sinauer Associates: Sunderland, MA.) is a branching diagram or a tree showing the evolutionary relationships among various biological spec ...
of close species.


Distribution


Range

The zebrafish is native to fresh water habitats in South Asia where it is found in India, Pakistan, Bangladesh, Nepal and Bhutan. The northern limit is in the South Himalayas, ranging from the
Sutlej The Sutlej or Satluj River () is the longest of the five rivers that flow through the historic crossroads region of Punjab in northern India and Pakistan. The Sutlej River is also known as ''Satadru''. It is the easternmost tributary of the Ind ...
river basin in the Pakistan–India border region to the state of Arunachal Pradesh in northeast Indian. Its range is concentrated in the Ganges and
Brahmaputra River The Brahmaputra is a trans-boundary river which flows through Tibet, northeast India, and Bangladesh. It is also known as the Yarlung Tsangpo in Tibetan, the Siang/Dihang River in Arunachali, Luit in Assamese, and Jamuna River in Bangla. It ...
basins, and the species was first described from
Kosi River The Kosi or Koshi ( ne, कोशी, , hi, कोसी, ) is a transboundary river which flows through China, Nepal and India. It drains the northern slopes of the Himalayas in Tibet and the southern slopes in Nepal. From a major confluence o ...
(lower Ganges basin) of India. Its range further south is more local, with scattered records from the Western and Eastern Ghats regions. It has frequently been said to occur in
Myanmar Myanmar, ; UK pronunciations: US pronunciations incl. . Note: Wikipedia's IPA conventions require indicating /r/ even in British English although only some British English speakers pronounce r at the end of syllables. As John C. Wells, Joh ...
(Burma), but this is entirely based on pre-1930 records and likely refers to close relatives only described later, notably ''
Danio kyathit ''Danio kyathit'' is a small, schooling species of fish in the family Cyprinidae. It is endemic to the upper reaches of Irrawaddy River near Myitkyina in northern Myanmar. Described in 1998, it is closely related to the better-known zebrafish ...
''. Likewise, old records from
Sri Lanka Sri Lanka (, ; si, ශ්‍රී ලංකා, Śrī Laṅkā, translit-std=ISO (); ta, இலங்கை, Ilaṅkai, translit-std=ISO ()), formerly known as Ceylon and officially the Democratic Socialist Republic of Sri Lanka, is an ...
are highly questionable and remain unconfirmed. Zebrafish have been introduced to California, Connecticut, Florida and New Mexico in the United States, presumably by deliberate release by aquarists or by escape from fish farms. The New Mexico population had been extirpated by 2003 and it is unclear if the others survive, as the last published records were decades ago. Elsewhere the species has been introduced to
Colombia Colombia (, ; ), officially the Republic of Colombia, is a country in South America with insular regions in North America—near Nicaragua's Caribbean coast—as well as in the Pacific Ocean. The Colombian mainland is bordered by the Car ...
and Malaysia.


Habitats

Zebrafish typically inhabit moderately flowing to stagnant clear water of quite shallow depth in streams, canals, ditches,
oxbow lake An oxbow lake is a U-shaped lake or pool that forms when a wide meander of a river is cut off, creating a free-standing body of water. In South Texas, oxbows left by the Rio Grande are called '' resacas''. In Australia, oxbow lakes are call ...
s, ponds and rice paddies. There is usually some vegetation, either submerged or overhanging from the banks, and the bottom is sandy, muddy or silty, often mixed with pebbles or gravel. In surveys of zebrafish locations throughout much of its Bangladeshi and Indian distribution, the water had a near-neutral to somewhat basic pH and mostly ranged from in temperature. One unusually cold site was only and another unusually warm site was , but the zebrafish still appeared healthy. The unusually cold temperature was at one of the highest known zebrafish locations at above sea level, although the species has been recorded to .


Description

The zebrafish is named for the five uniform, pigmented, horizontal, blue stripes on the side of the body, which are reminiscent of a zebra's stripes, and which extend to the end of the caudal fin. Its shape is
fusiform Fusiform means having a spindle-like shape that is wide in the middle and tapers at both ends. It is similar to the lemon-shape, but often implies a focal broadening of a structure that continues from one or both ends, such as an aneurysm on a b ...
and laterally compressed, with its mouth directed upwards. The male is torpedo-shaped, with gold stripes between the blue stripes; the female has a larger, whitish belly and silver stripes instead of gold. Adult females exhibit a small genital papilla in front of the
anal fin Fins are distinctive anatomical features composed of bony spines or rays protruding from the body of a fish. They are covered with skin and joined together either in a webbed fashion, as seen in most bony fish, or similar to a flipper, as se ...
origin. The zebrafish can reach up to in length, although they typically are in the wild with some variations depending on location. Its lifespan in captivity is around two to three years, although in ideal conditions, this may be extended to over five years. In the wild it is typically an annual species.


Psychology

In 2015, a study was published about zebrafishes' capacity for episodic memory. The individuals showed a capacity to remember context with respect to objects, locations and occasions (what, when, where). Episodic memory is a capacity of explicit memory systems, typically associated with conscious experience. The Mauthner cells integrate a wide array of sensory stimuli to produce the
escape reflex Escape reflex, or escape behavior, is any kind of escape response found in an animal when it is presented with an unwanted stimulus. It is a simple reflectory reaction in response to stimuli indicative of danger, that initiates an escape motion of ...
. Those stimuli are found to include the
lateral line The lateral line, also called the lateral line organ (LLO), is a system of sensory organs found in fish, used to detect movement, vibration, and pressure gradients in the surrounding water. The sensory ability is achieved via modified epithelial ...
signals by McHenry et al 2009 and visual signals consistent with looming objects by Temizer et al 2015, Dunn et al 2016, and Yao et al 2016.


Reproduction

The approximate generation time for ''Danio rerio'' is three months. A male must be present for ovulation and spawning to occur. Zebrafish are asynchronous spawners and under optimal conditions (such as food availability and favorable water parameters) can spawn successfully frequently, even on a daily basis. Females are able to spawn at intervals of two to three days, laying hundreds of eggs in each
clutch A clutch is a mechanical device that engages and disengages power transmission, especially from a drive shaft to a driven shaft. In the simplest application, clutches connect and disconnect two rotating shafts (drive shafts or line shafts). ...
. Upon release, embryonic development begins; in absence of sperm, growth stops after the first few cell divisions. Fertilized eggs almost immediately become transparent, a characteristic that makes ''D. rerio'' a convenient research
model species 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 workin ...
. Sex determination of common laboratory strains was shown to be a complex genetic trait, rather than to follow a simple ZW or XY system. The zebrafish embryo develops rapidly, with precursors to all major organs appearing within 36 hours of fertilization. The embryo begins as a yolk with a single enormous cell on top (see image, 0 h panel), which divides into two (0.75 h panel) and continues dividing until there are thousands of small cells (3.25 h panel). The cells then migrate down the sides of the yolk (8 h panel) and begin forming a head and tail (16 h panel). The tail then grows and separates from the body (24 h panel). The yolk shrinks over time because the fish uses it for food as it matures during the first few days (72 h panel). After a few months, the adult fish reaches reproductive maturity (bottom panel). To encourage the fish to spawn, some researchers use a fish tank with a sliding bottom insert, which reduces the depth of the pool to simulate the shore of a river. Zebrafish spawn best in the morning due to their Circadian rhythms. Researchers have been able to collect 10,000 embryos in 10 minutes using this method. In particular, one pair of adult fish is capable of laying 200–300 eggs in one morning in approximately 5 to 10 at time. Male zebrafish are furthermore known to respond to more pronounced markings on females, i.e., "good stripes", but in a group, males will mate with whichever females they can find. What attracts females is not currently understood. The presence of plants, even plastic plants, also apparently encourages spawning. Exposure to environmentally relevant concentrations of diisononyl phthalate (DINP), commonly used in a large variety of plastic items, disrupt the endocannabinoid system and thereby affect reproduction in a sex-specific manner.


Feeding

Zebrafish are omnivorous, primarily eating zooplankton,
phytoplankton Phytoplankton () are the autotrophic (self-feeding) components of the plankton community and a key part of ocean and freshwater ecosystems. The name comes from the Greek words (), meaning 'plant', and (), meaning 'wanderer' or 'drifter'. Ph ...
, insects and insect larvae, although they can eat a variety of other foods, such as worms and small crustaceans, if their preferred food sources are not readily available. In research, adult zebrafish are often fed with brine shrimp, or paramecia.


In the aquarium

Zebrafish are hardy fish and considered good for beginner aquarists. Their enduring popularity can be attributed to their playful disposition, as well as their rapid breeding, aesthetics, cheap price and broad availability. They also do well in schools or
shoals In oceanography, geomorphology, and geoscience, a shoal is a natural submerged ridge, bank, or bar that consists of, or is covered by, sand or other unconsolidated material and rises from the bed of a body of water to near the surface. It o ...
of six or more, and interact well with other fish species in the aquarium. However, they are susceptible to '' Oodinium'' or velvet disease, microsporidia (''Pseudoloma neurophilia''), and ''
Mycobacterium ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ('' M. tuberculosis'') and ...
'' species. Given the opportunity, adults eat hatchlings, which may be protected by separating the two groups with a net, breeding box or separate tank. In captivity, zebrafish live approximately forty-two months. Some captive zebrafish can develop a curved spine. The zebra danio was also used to make genetically modified fish and were the first species to be sold as GloFish (fluorescent colored fish).


Strains

In late 2003,
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 ...
zebrafish that express green, red, and yellow fluorescent proteins became commercially available in the United States. The fluorescent strains are tradenamed GloFish; other cultivated varieties include "golden", "sandy", "longfin" and "leopard". The leopard danio, previously known as ''Danio frankei'', is a spotted colour
morph Morph may refer to: Biology * Morph (zoology), a visual or behavioral difference between organisms of distinct populations in a species * Muller's morphs, a classification scheme for genetic mutations * "-morph", a suffix commonly used in tax ...
of the zebrafish which arose due to a pigment mutation. Xanthistic forms of both the zebra and leopard pattern, along with long-finned strains, have been obtained via selective breeding programs for the aquarium trade. Various transgenic and mutant strains of zebrafish were stored at the China Zebrafish Resource Center (CZRC), a non-profit organization, which was jointly supported by the Ministry of Science and Technology of China and the Chinese Academy of Sciences.


Wild-type strains

The Zebrafish Information Network ( ZFIN) provides up-to-date information about current known wild-type (WT) strains of ''D. rerio'', some of which are listed below. *''AB'' (AB) *''AB/C32'' (AB/C32) *''AB/TL'' (AB/TL) *''AB/Tuebingen'' (AB/TU) *''C32'' (C32) *''Cologne'' (KOLN) *''Darjeeling'' (DAR) *''Ekkwill'' (EKW) *''HK/AB'' (HK/AB) *''HK/Sing'' (HK/SING) *''Hong Kong'' (HK) *''India'' (IND) *''Indonesia'' (INDO) *''Nadia'' (NA) *''RIKEN WT'' (RW) *''Singapore'' (SING) *''SJA'' (SJA) *''SJD'' (SJD) *''SJD/C32'' (SJD/C32) *''Tuebingen'' (TU) *''Tupfel long fin'' (TL) *''Tupfel long fin nacre'' (TLN) *''WIK'' (WIK) *''WIK/AB'' (WIK/AB)


Hybrids

Hybrids between different ''Danio'' species may be fertile: for example, between ''D. rerio'' and '' D. nigrofasciatus''.


Scientific research

''D. rerio'' is a common and useful scientific
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 workin ...
for studies of vertebrate development and gene function. Its use as a laboratory animal was pioneered by the American
molecular biologist 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 ...
George Streisinger George Streisinger (December 27, 1927 – August 11, 1984) was an American molecular biologist and co-founder of the Institute of Molecular Biology at the University of Oregon. He was the first person to clone a vertebrate, cloning zebrafish in hi ...
and his colleagues at the University of Oregon in the 1970s and 1980s; Streisinger's zebrafish clones were among the earliest successful vertebrate clones created. Its importance has been consolidated by successful large-scale forward genetic screens (commonly referred to as the Tübingen/Boston screens). The fish has a dedicated online database of genetic, genomic, and developmental information, the Zebrafish Information Network (ZFIN). The Zebrafish International Resource Center (ZIRC) is a genetic resource repository with 29,250 alleles available for distribution to the research community. ''D. rerio'' is also one of the few fish species to have been sent into space. Research with ''D. rerio'' has yielded advances in the fields of
developmental biology Developmental biology is the study of the process by which animals and plants grow and develop. Developmental biology also encompasses the biology of Regeneration (biology), regeneration, asexual reproduction, metamorphosis, and the growth and di ...
, oncology, toxicology, reproductive studies, teratology, genetics, neurobiology,
environmental science Environmental science is an interdisciplinary academic field that integrates physics, biology, and geography (including ecology, chemistry, plant science, zoology, mineralogy, oceanography, limnology, soil science, geology and physical geograp ...
s,
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
research, regenerative medicine,
muscular dystrophies 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 ...
and evolutionary theory.


Model characteristics

As a model biological system, the zebrafish possesses numerous advantages for scientists. Its genome has been fully sequenced, and it has well-understood, easily observable and testable developmental behaviors. Its
embryonic development An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
is very rapid, and its embryos are relatively large, robust, and transparent, and able to develop outside their mother. Furthermore, well-characterized mutant strains are readily available. Other advantages include the species' nearly constant size during early development, which enables simple
staining Staining is a technique used to enhance contrast in samples, generally at the microscopic level. Stains and dyes are frequently used in histology (microscopic study of biological tissues), in cytology (microscopic study of cells), and in the ...
techniques to be used, and the fact that its two-celled embryo can be fused into a single cell to create a homozygous embryo. The zebrafish is also demonstrably similar to mammalian models and humans in toxicity testing, and exhibits a diurnal sleep cycle with similarities to mammalian sleep behavior. However, zebrafish are not a universally ideal research model; there are a number of disadvantages to their scientific use, such as the absence of a standard diet and the presence of small but important differences between zebrafish and mammals in the roles of some genes related to human disorders.


Regeneration

Zebrafish have the ability to regenerate their heart and
lateral line The lateral line, also called the lateral line organ (LLO), is a system of sensory organs found in fish, used to detect movement, vibration, and pressure gradients in the surrounding water. The sensory ability is achieved via modified epithelial ...
hair cells during their larval stages. The cardiac regenerative process likely involves signaling pathways such as Notch and Wnt; hemodynamic changes in the damaged heart are sensed by ventricular endothelial cells and their associated cardiac cilia by way of the mechanosensitive ion channel
TRPV4 Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the ''TRPV4'' gene. The ''TRPV4'' gene encodes TRPV4, initially named "vanilloid-receptor related osmotically activated channe ...
, subsequently facilitating the
Notch signaling pathway The Notch signaling pathway is a highly Conserved sequence, conserved cell signaling system present in most animals. Mammals possess four different Notch proteins, notch receptors, referred to as NOTCH1, NOTCH2, Notch 3, NOTCH3, and NOTCH4. The ...
via KLF2 and activating various downstream effectors such as BMP-2 and HER2/neu. In 2011, the British Heart Foundation ran an advertising campaign publicising its intention to study the applicability of this ability to humans, stating that it aimed to raise £50 million in research funding. Zebrafish have also been found to regenerate photoreceptor cells and retinal neurons following injury, which has been shown to be mediated by the dedifferentiation and proliferation of
Müller glia Müller glia, or Müller cells, are a type of retinal glial cells, first recognized and described by Heinrich Müller. They are found in the vertebrate retina, where they serve as support cells for the neurons, as all glial cells do. They are the ...
. Researchers frequently
amputate Amputation is the removal of a limb by trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on indi ...
the dorsal and ventral tail fins and analyze their regrowth to test for mutations. It has been found that histone demethylation occurs at the site of the amputation, switching the zebrafish's cells to an "active", regenerative, stem cell-like state. In 2012, Australian scientists published a study revealing that zebrafish use a specialised protein, known as fibroblast growth factor, to ensure their spinal cords heal without glial scarring after injury. In addition, hair cells of the posterior
lateral line The lateral line, also called the lateral line organ (LLO), is a system of sensory organs found in fish, used to detect movement, vibration, and pressure gradients in the surrounding water. The sensory ability is achieved via modified epithelial ...
have also been found to regenerate following damage or developmental disruption. Study of gene expression during regeneration has allowed for the identification of several important signaling pathways involved in the process, such as
Wnt signaling 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 p ...
and Fibroblast growth factor. In probing disorders of the nervous system, including neurodegenerative diseases, movement disorders, psychiatric disorders and deafness, researchers are using the zebrafish to understand how the genetic defects underlying these conditions cause functional abnormalities in the human brain, spinal cord and sensory organs. Researchers have also studied the zebrafish to gain new insights into the complexities of human musculoskeletal diseases, such as
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 ...
. Another focus of zebrafish research is to understand how a gene called Hedgehog, a biological signal that underlies a number of human cancers, controls cell growth.


Genetics


Background genetics

Inbred strains and traditional outbred stocks have not been developed for laboratory zebrafish, and the genetic variability of wild-type lines among institutions may contribute to the replication crisis in biomedical research. Genetic differences in wild-type lines among populations maintained at different research institutions have been demonstrated using both Single-nucleotide polymorphisms and
microsatellite A microsatellite is a tract of repetitive DNA in which certain DNA motifs (ranging in length from one to six or more base pairs) are repeated, typically 5–50 times. Microsatellites occur at thousands of locations within an organism's genome. ...
analysis.


Gene expression

Due to their fast and short life cycles and relatively large clutch sizes, ''D. rerio'' or zebrafish are a useful model for genetic studies. A common reverse genetics technique is to reduce gene expression or modify splicing using Morpholino antisense technology. Morpholino oligonucleotides (MO) are stable, synthetic
macromolecule A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...
s that contain the same bases as DNA or RNA; by binding to complementary RNA sequences, they can reduce the expression of specific genes or block other processes from occurring on RNA. MO can be injected into one cell of an embryo after the 32-cell stage, reducing gene expression in only cells descended from that cell. However, cells in the early embryo (less than 32 cells) are interpermeable to large molecules, allowing diffusion between cells. Guidelines for using Morpholinos in zebrafish describe appropriate control strategies. Morpholinos are commonly microinjected in 500pL directly into 1-2 cell stage zebrafish embryos. The morpholino is able to integrate into most cells of the embryo. A known problem with gene knockdowns is that, because the genome underwent a duplication after the divergence of ray-finned fishes and lobe-finned fishes, it is not always easy to silence the activity of one of the two gene paralogs reliably due to complementation by the other paralog. Despite the complications of the zebrafish genome, a number of commercially available global platforms exist for analysis of both gene expression by microarrays and promoter regulation using ChIP-on-chip.


Genome sequencing

The Wellcome Trust Sanger Institute started the zebrafish genome sequencing project in 2001, and the full genome sequence of the Tuebingen reference strain is publicly available at the National Center for Biotechnology Information (NCBI)'
Zebrafish Genome Page
The zebrafish reference genome sequence is annotated as part of the Ensemblbr>project
and is maintained by the Genome Reference Consortium. In 2009, researchers at the Institute of Genomics and Integrative Biology in Delhi, India, announced the sequencing of the genome of a wild zebrafish strain, containing an estimated 1.7 billion genetic letters. The genome of the wild zebrafish was sequenced at 39-fold coverage. Comparative analysis with the zebrafish reference genome revealed over 5 million single nucleotide variations and over 1.6 million insertion deletion variations. The zebrafish reference genome sequence of 1.4GB and over 26,000 protein coding genes was published by Kerstin Howe ''et al.'' in 2013.


Mitochondrial DNA

In October 2001, researchers from the University of Oklahoma published ''D. rerio's'' complete
mitochondrial DNA Mitochondrial DNA (mtDNA or mDNA) is the DNA located in mitochondria, cellular organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use, such as adenosine triphosphate (ATP). Mitochondrial D ...
sequence. Its length is 16,596 base pairs. This is within 100 base pairs of other related species of fish, and it is notably only 18 pairs longer than the goldfish (''Carassius auratus'') and 21 longer than the
carp Carp are various species of oily freshwater fish from the family Cyprinidae, a very large group of fish native to Europe and Asia. While carp is consumed in many parts of the world, they are generally considered an invasive species in parts of ...
(''Cyprinus carpio''). Its gene order and content are identical to the common vertebrate form of mitochondrial DNA. It contains 13 protein-coding genes and a noncoding control region containing the origin of replication for the heavy strand. In between a grouping of five tRNA genes, a sequence resembling vertebrate origin of light strand replication is found. It is difficult to draw evolutionary conclusions because it is difficult to determine whether base pair changes have adaptive significance via comparisons with other vertebrates' nucleotide sequences.


Developmental genetics

T-boxes and
homeobox A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. For instance, mutations in a homeobox may change large-scale anatomical features of the full- ...
es are vital in ''Danio'' similarly to other vertebrates. The Bruce et al team are known for this area, and in Bruce et al 2003 & Bruce et al 2005 uncover the role of two of these elements in oocytes of this species. By interfering via a dominant nonfunctional allele and a morpholino they find the T-box transcription activator
Eomesodermin Eomesodermin also known as T-box brain protein 2 (Tbr2) is a protein that in humans is encoded by the ''EOMES'' gene. The Eomesodermin/Tbr2 gene, ''EOMES'', encodes a member of a conserved protein family that shares a common DNA-binding domain ...
and its target '' mtx2'' – a transcription factor – are vital to epiboly. (In Bruce et al 2003 they failed to support the possibility that Eomesodermin behaves like Vegt. Neither they nor anyone else has been able to locate any mutation which – in the mother – will prevent initiation of the
mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...
or
endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gast ...
development processes in this species.)


Pigmentation genes

In 1999, the ''nacre'' mutation was identified in the zebrafish ortholog of the mammalian ''MITF'' transcription factor. Mutations in human ''
MITF Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the ''MITF'' gene. MITF is a basic helix-loop-helix leucine zipper transcription factor ...
'' result in eye defects and loss of pigment, a type of Waardenburg Syndrome. In December 2005, a study of the ''golden'' strain identified the gene responsible for its unusual pigmentation as SLC24A5, a solute carrier that appeared to be required for melanin production, and confirmed its function with a Morpholino knockdown. The
orthologous 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 spec ...
gene was then characterized in humans and a one base pair difference was found to strongly segregate fair-skinned Europeans and dark-skinned Africans. Zebrafish with the ''nacre'' mutation have since been bred with fish with a ''roy orbison (roy)'' mutation to make fish that have no melanophores or iridophores, and are transparent into adulthood. These fish are characterized by uniformly pigmented eyes and translucent skin.


Transgenesis

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 ...
sis is a popular approach to study the function of genes in zebrafish. Construction of transgenic zebrafish is rather easy by a method using the ''Tol2'' transposon system. ''Tol2'' element which encodes a gene for a fully functional transposase capable of catalyzing transposition in the zebrafish germ lineage. ''Tol2'' is the only natural DNA transposable element in vertebrates from which an autonomous member has been identified. Examples include the artificial interaction produced between
LEF1 Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the ''LEF1'' gene. It's a member of T cell factor/lymphoid enhancer factor ( TCF/LEF) family. Function Lymphoid enhancer-binding factor-1 (LEF1) is a 48-kD nu ...
and Catenin beta-1/β-catenin/''CTNNB1''. Dorsky et al 2002 investigated the developmental role of Wnt by transgenically expressing a Lef1/β-catenin reporter. There are well-established protocols for editing zebrafish genes using
CRISPR-Cas9 Cas9 (CRISPR associated protein 9, formerly called Cas5, Csn1, or Csx12) is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic ...
and this tool has been used to generate genetically modified models.


Transparent adult bodies

In 2008, researchers at Boston Children's Hospital developed a new strain of zebrafish, named Casper, whose adult bodies had transparent skin. This allows for detailed visualization of cellular activity, circulation, metastasis and many other phenomena. In 2019 researchers published a crossing of a ''prkdc-/-'' and a ''IL2rga-/-'' strain that produced transparent, immunodeficient offspring, lacking
natural killer cell Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and repres ...
s as well as B- and
T-cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...
. This strain can be adapted to warm water and the absence of an immune system makes the use of patient derived
xenografts 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 ...
possible. In January 2013, Japanese scientists genetically modified a transparent zebrafish specimen to produce a visible glow during periods of intense brain activity. In January 2007, Chinese researchers at Fudan University genetically modified zebrafish to detect
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 activ ...
pollution in lakes and rivers, which is linked to male infertility. The researchers cloned oestrogen-sensitive genes and injected them into the fertile eggs of zebrafish. The modified fish turned green if placed into water that was polluted by oestrogen."Fudan scientists turn fish into estrogen alerts"
Xinhua. January 12, 2007. Retrieved November 15, 2012.


RNA splicing

In 2015, researchers at
Brown University Brown University is a private research university in Providence, Rhode Island. Brown is the seventh-oldest institution of higher education in the United States, founded in 1764 as the College in the English Colony of Rhode Island and Providenc ...
discovered that 10% of zebrafish genes do not need to rely on the U2AF2 protein to initiate
RNA splicing RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing all the introns (non-coding regions of RNA) and ''splicing'' b ...
. These genes have the DNA base pairs AC and TG as repeated sequences at the ends of each
intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...
. On the 3'ss (3' splicing site), the base pairs adenine and cytosine alternate and repeat, and on the 5'ss (5' splicing site), their complements thymine and guanine alternate and repeat as well. They found that there was less reliance on U2AF2 protein than in humans, in which the protein is required for the splicing process to occur. The pattern of repeating base pairs around introns that alters RNA
secondary structure Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...
was found in other teleosts, but not in tetrapods. This indicates that an evolutionary change in tetrapods may have led to humans relying on the U2AF2 protein for RNA splicing while these genes in zebrafish undergo splicing regardless of the presence of the protein.


Orthology

''D. rerio'' has three transferrins, all of which cluster closely with other vertebrates.


Inbreeding depression

When close relatives mate, progeny may exhibit the detrimental effects of inbreeding depression. Inbreeding depression is predominantly caused by the homozygous expression of recessive deleterious alleles. For zebrafish, inbreeding depression might be expected to be more severe in stressful environments, including those caused by anthropogenic pollution. Exposure of zebrafish to environmental stress induced by the chemical clotrimazole, an imidazole fungicide used in agriculture and in veterinary and human medicine, amplified the effects of inbreeding on key reproductive traits. Embryo viability was significantly reduced in inbred exposed fish and there was a tendency for inbred males to sire fewer offspring.


Aquaculture research

Zebrafish are common models for research into fish farming, including pathogens and parasites causing yield loss and/or spread to adjacent wild populations. This usefulness is less than it might be due to ''Danio''s
taxonomic Taxonomy is the practice and science of categorization or classification. A taxonomy (or taxonomical classification) is a scheme of classification, especially a hierarchical classification, in which things are organized into groups or types. ...
distance from the most common aquaculture species. Because the most common are
salmonid Salmonidae is a family of ray-finned fish that constitutes the only currently extant family in the order Salmoniformes . It includes salmon (both Atlantic and Pacific species), trout (both ocean-going and landlocked), chars, freshwater whitefis ...
s and
cod Cod is the common name for the demersal fish genus '' Gadus'', belonging to the family Gadidae. Cod is also used as part of the common name for a number of other fish species, and one species that belongs to genus ''Gadus'' is commonly not call ...
in the Protacanthopterygii and
sea bass Sea bass is a common name for a variety of different species of marine fish. Many fish species of various families have been called sea bass. In Ireland and the United Kingdom, the fish sold and consumed as sea bass is exclusively the European ba ...
,
sea bream The Sparidae are a family of fish in the order Perciformes, commonly called sea breams and porgies. The sheepshead, scup, and red seabream are species in this family. Most sparids are deep-bodied compressed fish with a small mouth separated by a ...
, tilapia, and
flatfish A flatfish is a member of the Ray-finned fish, ray-finned demersal fish order (biology), order Pleuronectiformes, also called the Heterosomata, sometimes classified as a suborder of Perciformes. In many species, both eyes lie on one side of the ...
, in the Percomorpha, zebrafish results may not be perfectly applicable. Various other
models A model is an informative representation of an object, person or system. The term originally denoted the plans of a building in late 16th-century English, and derived via French and Italian ultimately from Latin ''modulus'', a measure. Models c ...
Goldfish (''
Carassius auratus The goldfish (''Carassius auratus'') is a freshwater fish in the family Cyprinidae of order Cypriniformes. It is commonly kept as a pet in indoor aquariums, and is one of the most popular aquarium fish. Goldfish released into the wild have ...
''), Medaka ('' Oryzias latipes''), Stickleback (''
Gasterosteus aculeatus The three-spined stickleback (''Gasterosteus aculeatus'') is a fish native to most inland and coastal waters north of 30°N. It has long been a subject of scientific study for many reasons. It shows great morphological variation throughout its ra ...
''), Roach ('' Rutilus rutilus''), Pufferfish ('' Takifugu rubripes''), Swordtail (''
Xiphophorus hellerii ''Xiphophorus'' is a genus of euryhaline and freshwater fishes in the family Poeciliidae of order Cyprinodontiformes, native to Mexico and northern Central America. The many ''Xiphophorus'' species are all known as platyfish (or platies) and ...
'') are less used normally but would be closer to particular target species. The only exception are the
Carp Carp are various species of oily freshwater fish from the family Cyprinidae, a very large group of fish native to Europe and Asia. While carp is consumed in many parts of the world, they are generally considered an invasive species in parts of ...
(including Grass Carp, '' Ctenopharyngodon idella'') and Milkfish ('' Chanos chanos'') which are quite close, both being in the
Cyprinidae Cyprinidae is a family of freshwater fish commonly called the carp or minnow family. It includes the carps, the true minnows, and relatives like the barbs and barbels. Cyprinidae is the largest and most diverse fish family and the largest verte ...
. However it should also be noted that ''Danio'' consistently proves to be a useful model for mammals in many cases and there is dramatically more genetic distance between them than between ''Danio'' and any farmed fish.


Neurochemistry

In a glucocorticoid receptor-defective mutant with reduced exploratory behavior,
fluoxetine Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorde ...
rescued the normal exploratory behavior. This demonstrates relationships between glucocorticoids, fluoxetine, and exploration in this fish.


Drug discovery and development

The zebrafish and zebrafish larva is a suitable model organism for drug discovery and development. As a vertebrate with 70% genetic homology with humans, it can be predictive of human health and disease, while its small size and fast development facilitates experiments on a larger and quicker scale than with more traditional in vivo studies, including the development of higher-throughput, automated investigative tools. As demonstrated through ongoing research programmes, the zebrafish model enables researchers not only to identify genes that might underlie human disease, but also to develop novel therapeutic agents in drug discovery programmes. Zebrafish embryos have proven to be a rapid, cost-efficient, and reliable teratology assay model.


Drug screens

Drug screens in zebrafish can be used to identify novel classes of compounds with biological effects, or to repurpose existing drugs for novel uses; an example of the latter would be a screen which found that a commonly used statin (
rosuvastatin Rosuvastatin, sold under the brand name Crestor among others, is a statin medication, used to prevent cardiovascular disease in those at high risk and treat abnormal lipids. It is recommended to be used together with dietary changes, exercise, ...
) can suppress the growth of
prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
. To date, 65 small-molecule screens have been carried out and at least one has led to clinical trials. Within these screens, many technical challenges remain to be resolved, including differing rates of drug absorption resulting in levels of internal exposure that cannot be extrapolated from the water concentration, and high levels of natural variation between individual animals.


Toxico- or pharmacokinetics

To understand drug effects, the internal drug exposure is essential, as this drives the pharmacological effect. Translating experimental results from zebrafish to higher vertebrates (like humans) requires concentration-effect relationships, which can be derived from
pharmacokinetic Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
and
pharmacodynamic Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (for ...
analysis. Because of its small size, however, it is very challenging to quantify the internal drug exposure. Traditionally multiple blood samples would be drawn to characterize the drug concentration profile over time, but this technique remains to be developed. To date, only a single pharmacokinetic model for
paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
has been developed in zebrafish larvae.


Computational data analysis

Using smart data analysis methods, pathophysiological and pharmacological processes can be understood and subsequently translated to higher vertebrates, including humans. An example is the use of
systems pharmacology Systems pharmacology is the application of systems biology principles to the field of pharmacology. It seeks to understand how drugs affect the human body as a single complex biological system. Instead of considering the effect of a drug to be the ...
, which is the integration of
systems biology Systems biology is the computational modeling, computational and mathematical analysis and modeling of complex biological systems. It is a biology-based interdisciplinary field of study that focuses on complex interactions within biological syst ...
and
pharmacometrics Pharmacometrics is a field of study of the methodology and application of models for disease and pharmacological measurement. It uses mathematical models of biology, pharmacology, disease, and physiology to describe and quantify interactions between ...
. Systems biology characterizes (part of) an organism by a mathematical description of all relevant processes. These can be for example different signal transduction pathways that upon a specific signal lead to a certain response. By quantifying these processes, their behaviour in healthy and diseased situation can be understood and predicted. Pharmacometrics uses data from preclinical experiments and
clinical trials Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
to characterize the pharmacological processes that are underlying the relation between the drug dose and its response or clinical outcome. These can be for example the drug
absorption Absorption may refer to: Chemistry and biology * Absorption (biology), digestion **Absorption (small intestine) *Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials *Absorption (skin), a route by which ...
in or clearance from the body, or its interaction with the target to achieve a certain effect. By quantifying these processes, their behaviour after different doses or in different patients can be understood and predicted to new doses or patients. By integrating these two fields, systems pharmacology has the potential to improve the understanding of the interaction of the drug with the biological system by mathematical quantification and subsequent prediction to new situations, like new drugs or new organisms or patients. Using these computational methods, the previously mentioned analysis of paracetamol internal exposure in zebrafish larvae showed reasonable correlation between paracetamol clearance in zebrafish with that of higher vertebrates, including humans.


Medical research


Cancer

Zebrafish have been used to make several transgenic models of cancer, including
melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
, leukemia,
pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of t ...
and
hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in t ...
. Zebrafish expressing mutated forms of either the BRAF or NRAS oncogenes develop melanoma when placed onto a p53 deficient background. Histologically, these tumors strongly resemble the human disease, are fully transplantable, and exhibit large-scale genomic alterations. The BRAF melanoma model was utilized as a platform for two screens published in March 2011 in the journal ''Nature''. In one study, the model was used as a tool to understand the functional importance of genes known to be amplified and overexpressed in human melanoma. One gene, SETDB1, markedly accelerated tumor formation in the zebrafish system, demonstrating its importance as a new melanoma oncogene. This was particularly significant because SETDB1 is known to be involved in the epigenetic regulation that is increasingly appreciated to be central to tumor cell biology. In another study, an effort was made to therapeutically target the genetic program present in the tumor's origin neural crest cell using a chemical screening approach. This revealed that an inhibition of the DHODH protein (by a small molecule called leflunomide) prevented development of the neural crest stem cells which ultimately give rise to melanoma via interference with the process of transcriptional elongation. Because this approach would aim to target the "identity" of the melanoma cell rather than a single genetic mutation, leflunomide may have utility in treating human melanoma.


Cardiovascular disease

In cardiovascular research, the zebrafish has been used to model human myocardial infarction model. The zebrafish heart completely regenerates after about 2 months of injury without any scar formation. Zebrafish is also used as a model for blood clotting, blood vessel development, and congenital heart and kidney disease.


Immune system

In programmes of research into acute inflammation, a major underpinning process in many diseases, researchers have established a zebrafish model of inflammation, and its resolution. This approach allows detailed study of the genetic controls of inflammation and the possibility of identifying potential new drugs. Zebrafish has been extensively used as a model organism to study vertebrate innate immunity. The innate immune system is capable of phagocytic activity by 28 to 30 h postfertilization (hpf) while adaptive immunity is not functionally mature until at least 4 weeks postfertilization.


Infectious diseases

As the immune system is relatively conserved between zebrafish and humans, many human infectious diseases can be modeled in zebrafish. The transparent early life stages are well suited for ''in vivo'' imaging and genetic dissection of host-pathogen interactions. Zebrafish models for a wide range of bacterial, viral and parasitic pathogens have already been established; for example, the zebrafish model for tuberculosis provides fundamental insights into the mechanisms of pathogenesis of mycobacteria. Furthermore, robotic technology has been developed for high-throughput antimicrobial drug screening using zebrafish infection models.


Repairing retinal damage

Another notable characteristic of the zebrafish is that it possesses four types of
cone cell Cone cells, or cones, are photoreceptor cells in the retinas of vertebrate eyes including the human eye. They respond differently to light of different wavelengths, and the combination of their responses is responsible for color vision. Cone ...
, with ultraviolet-sensitive cells supplementing the red, green and blue cone cell subtypes found in humans. Zebrafish can thus observe a very wide spectrum of colours. The species is also studied to better understand the development of the retina; in particular, how the cone cells of the retina become arranged into the so-called 'cone mosaic'. Zebrafish, in addition to certain other teleost fish, are particularly noted for having extreme precision of cone cell arrangement. This study of the zebrafish's retinal characteristics has also extrapolated into medical enquiry. In 2007, researchers at University College London grew a type of zebrafish adult
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...
found in the eyes of fish and mammals that develops into neurons in the retina. These could be injected into the eye to treat diseases that damage retinal neurons—nearly every disease of the eye, including macular degeneration, glaucoma, and diabetes-related blindness. The researchers studied Müller glial cells in the eyes of humans aged from 18 months to 91 years, and were able to develop them into all types of retinal neurons. They were also able to grow them easily in the lab. The stem cells successfully migrated into diseased rats' retinas, and took on the characteristics of the surrounding neurons. The team stated that they intended to develop the same approach in humans.


Muscular dystrophies

Muscular dystrophies 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 ...
(MD) are a heterogeneous group of genetic disorders that cause muscle weakness, abnormal contractions and muscle wasting, often leading to premature death. Zebrafish is widely used as model organism to study muscular dystrophies. For example, the ''sapje'' (''sap'') mutant is the zebrafish orthologue of human Duchenne muscular dystrophy (DMD). The Machuca-Tzili and co-workers applied zebrafish to determine the role of alternative splicing factor, MBNL, in myotonic dystrophy type 1 (DM1) pathogenesis. More recently, Todd et al. described a new zebrafish model designed to explore the impact of CUG repeat expression during early development in DM1 disease. Zebrafish is also an excellent animal model to study congenital muscular dystrophies including CMD Type 1 A (CMD 1A) caused by mutation in the human laminin α2 (LAMA2) gene. The zebrafish, because of its advantages discussed above, and in particular the ability of zebrafish embryos to absorb chemicals, has become a model of choice in screening and testing new drugs against muscular dystrophies.


Bone physiology and pathology

Zebrafish have been used as model organisms for bone metabolism, tissue turnover, and resorbing activity. These processes are largely evolutionary conserved. They have been used to study osteogenesis (bone formation), evaluating differentiation, matrix deposition activity, and cross-talk of skeletal cells, to create and isolate mutants modeling human bone diseases, and test new chemical compounds for the ability to revert bone defects. The larvae can be used to follow new (''de novo'') osteoblast formation during bone development. They start mineralising bone elements as early as 4 days post fertilisation. Recently, adult zebrafish are being used to study complex age related bone diseases such as
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
and osteogenesis imperfecta. The (elasmoid) scales of zebrafish function as a protective external layer and are little bony plates made by osteoblasts. These exoskeletal structures are formed by bone matrix depositing osteoblasts and are remodeled by osteoclasts. The scales also act as the main calcium storage of the fish. They can be cultured ex-vivo (kept alive outside of the organism) in a multi-well plate, which allows manipulation with drugs and even screening for new drugs that could change bone metabolism (between osteoblasts and osteoclasts).


Diabetes

Zebrafish pancreas development is very homologous to mammals, such as mice. The signaling mechanisms and way the pancreas functions are very similar. The pancreas has an endocrine compartment, which contains a variety of cells. Pancreatic PP cells that produce polypeptides, and β-cells that produce insulin are two examples of those such cells. This structure of the pancreas, along with the glucose homeostasis system, are helpful in studying diseases, such as diabetes, that are related to the pancreas. Models for pancreas function, such as fluorescent staining of proteins, are useful in determining the processes of glucose homeostasis and the development of the pancreas. Glucose tolerance tests have been developed using zebrafish, and can now be used to test for glucose intolerance or diabetes in humans. The function of insulin are also being tested in zebrafish, which will further contribute to human medicine. The majority of work done surrounding knowledge on glucose homeostasis has come from work on zebrafish transferred to humans.


Obesity

Zebrafish have been used as a model system to study obesity, with research into both genetic obesity and over-nutrition induced obesity. Obese zebrafish, similar to obese mammals, show dysregulation of lipid controlling metabolic pathways, which leads to weight gain without normal lipid metabolism. Also like mammals, zebrafish store excess lipids in visceral, intramuscular, and subcutaneous adipose deposits. These reasons and others make zebrafish good models for studying obesity in humans and other species. Genetic obesity is usually studied in transgenic or mutated zebrafish with obesogenic genes. As an example, transgenic zebrafish with overexpressed AgRP, an endogenous melacortin antagonist, showed increased body weight and adipose deposition during growth. Though zebrafish genes may not be the exact same as human genes, these tests could provide important insight into possible genetic causes and treatments for human genetic obesity. Diet-induced obesity zebrafish models are useful, as diet can be modified from a very early age. High fat diets and general overfeeding diets both show rapid increases in adipose deposition, increased BMI, hepatosteatosis, and hypertriglyceridemia. However, the normal fat, overfed specimens are still metabolically healthy, while high-fat diet specimens are not. Understanding differences between types of feeding-induced obesity could prove useful in human treatment of obesity and related health conditions.


Environmental toxicology

Zebrafish have been used as a model system in environmental toxicology studies.


Epilepsy

Zebrafish have been used as a model system to study epilepsy. Mammalian seizures can be recapitulated molecularly, behaviorally, and electrophysiologically, using a fraction of the resources required for experiments in mammals.


See also

*
Japanese rice fish The Japanese rice fish (''Oryzias latipes''), also known as the medaka, is a member of genus ''Oryzias'' ( ricefish), the only genus in the subfamily Oryziinae. This small (up to about ) native of East Asia is a denizen of rice paddies, marshes, ...
or medaka, another fish used for genetic, developmental, and biomedical research *
List of freshwater aquarium fish species A vast number of aquatic species have successfully adapted to live in the freshwater aquarium. This list gives some examples of the most common species found in home aquariums. Catfish Characins and other characiformes ...
*
ZebraBox The ZebraBox is an automated analysis chamber for the non-intrusive video observation of different types of freshwater marine indicator species, such as ''Dania rerio'' and ''Pimephales promelas''. It is a type of Larval Photomoter Response (LPR) a ...
, a specialised container for the scientific study of zebrafish


References


Further reading

* * * * * * *


External links


British Association of Zebrafish Husbandry

International Zebrafish Society
(IZFS)
European Society for Fish Models in Biology and Medicine
(EuFishBioMed)
The Zebrafish Information Network
(ZFIN)
The Zebrafish International Resource Center
(ZIRC)
The European Zebrafish Resource Center
(EZRC)
The China Zebrafish Resource Center
(CZRC)
The Zebrafish Genome Sequencing Project
at the Wellcome Trust Sanger Institute
FishMap: The Zebrafish Community Genomics Browser
at the Institute of Genomics and Integrative Biology (IGIB)
WebHome Zebrafish GenomeWiki Beta Preview
at the IGIB
Genome sequencing initiative
at the IGIB
''Danio rerio''
at Danios.info
Sanger Institute Zebrafish Mutation Resource

Zebrafish genome
via Ensembl
FishforScience.com
– using zebrafish for medical research
FishForPharma

Breeding Zebrafish
* {{Taxonbar, from=Q169444 Fish described in 1822 Danio Fish of Bangladesh Freshwater fish of India Fish of Pakistan Animal models Stem cell research Regenerative biomedicine Animal models in neuroscience Taxa named by Francis Buchanan-Hamilton