Danio rerio
Encyclopedia
The zebrafish, Danio rerio, is a tropical freshwater fish
belonging to the minnow family
(Cyprinidae) of order
Cypriniformes
. It is a popular aquarium fish
, frequently sold under the trade name zebra danio, and is an important vertebrate model organism
in scientific research.
member of the genus Danio
. It has a sister group
relationship with Danio kyathit
.
Zebrafish are closely related to the genus Devario
, as demonstrated by a phylogenetic tree
of close species.
region, including the countries India
, Pakistan
, Bangladesh
, Nepal
, and Myanmar
. It arose in the Ganges region in eastern India
, and commonly inhabits streams, canals, ditches, ponds, and slow-moving to stagnant water bodies, including rice fields.
Zebrafish have been introduced
to parts of the United States
, presumably by deliberate release or by escape from fish farms. They have also been sighted in Colombia
.
-shaped and have gold stripes between the blue stripes; females have a larger, whitish belly and have silver stripes instead of gold. Adult females will exhibit a small genital papilla in front of the anal fin origin. The zebrafish can grow to 6.4 centimetres (2.5 in), although it is uncommon for them to grow past 4 cm in captivity. Life-span in captivity is around 2–3 years, although in ideal conditions, may extend to 5 years.
to occur. Females are able to spawn at intervals of 2–3 days, laying hundreds of eggs in each clutch
. Upon release, embryonic development begins; absent 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
. Development progresses rapidly. Precursors to all major organs appear within 36 hours of fertilization, and hatching takes place 12-36 hours later, depending on the embryo's internal conditions and the external temperature, ideally 28.5 °C (83.3 °F). Swimming and feeding behavior begin about 36 hours later. The sex of juveniles cannot be distinguished except by dissection, and sex determinants are not clearly understood.
, insect
s, insect larva
e, and phytoplankton
. It can eat a variety of other foods, such as worm
s and small crustacean
s if its preferred sources are not readily available. Most danios accept common food flakes and tubifex worms in the aquarium
.
, red, and yellow fluorescent protein
s. They 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 of the zebrafish caused by a pigment mutation. Xanthistic
forms of both the zebra
and leopard
pattern, along with long-finned subspecies, have been obtained via selective breeding programs for the aquarium trade.
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)
. Their decades of popularity can also be attributed to their playful disposition, as well as their rapid breeding, beauty, price, and broad availability. They thrive best in 22–28 °C (71.6–82.4 F) water. They need an aquarium of 10 gallons (37.9 l) or more, and they do well in schools. They also thrive as shoals
of six or more, and interact well with other fish types in the aquarium. However, they are susceptible to Oodinium
or velvet disease, microsporidia
(Pseudoloma neurophilia), and Mycobacterium
species. Given the opportunity, adults eat hatchlings, which may be protected by separating the two groups with a net, breeding box or separate tank.
D. rerio is a common and useful model organism
for studies of vertebrate
development and gene
function. George Streisinger
at the University of Oregon
established its utility. Success with it in large scale forward genetic screen
s (commonly referred to as the Tübingen/Boston screens) consolidated its importance. The scholarly journal Development devoted an issue to research using it in celebration of this landmark. It has a dedicated online database of genetic, genomic, and developmental information, the Zebrafish Information Network
(ZFIN). D. rerio is one of the few fish species to have reached space
. They may supplement higher vertebrate models, such as rats and mice.
Research with D. rerio has allowed advances in the fields of developmental biology
, oncology
, toxicology
, reproductive studies, teratology
, genetics
, neurobiology, environmental science
s, stem cell
and regenerative medicine
, and evolutionary theory.
Other advantages:
fins, skin, the heart and the brain (in larval stages). Heart muscle regeneration does not make use of stem cell
s; instead, mature heart muscle cells regress to a stem-cell-like state and redifferentiate. In 2011, the British Heart Foundation
ran an advertising campaign (including on television and on line) publicising their intention to study the applicability of this ability to humans by "spend[ing] £50 million on a programme of groundbreaking research that could help us begin to repair damaged [human] hearts."
Zebrafish have also been found to regenerate photoreceptor cells and retina
l neurons following injury. The mechanisms of this regeneration are unknown. Researchers frequently amputate the dorsal and ventral tail fins and analyze their regrowth to test for mutations. This research is leading the scientific community in the understanding of healing/repair mechanisms in vertebrates. It has also been found if the same fin is damaged enough times, the fish will grow a new fin which will have mutated only a small amount. Most scientists believe this is a defence mechanism to try to prevent the fin from being damaged again.
technique is to reduce gene expression
or modify splicing
using Morpholino
antisense technology. Morpholino oligonucleotide
s (MO) are stable, synthetic macromolecules that contain the same bases as DNA or RNA; by binding to complementary RNA sequences, they reduce the expression
of specific genes. The journal Genesis devoted an issue to research using MO, mostly in D. rerio. 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. 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 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 for analysis of both gene expression by microarrays
and promoter regulation using ChIP-on-chip
exist.
, Delhi
announced the sequencing of a wild caught strain, containing 1.7 billion
genetic letters.
published D. rerio's complete mitochondrial DNA
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
(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.
, a solute
carrier that appeared to be required for melanin
production, and confirmed its function with a Morpholino knockdown. The orthologous gene was then characterized in humans and a one base pair difference was found to strongly segregate fair-skinned Europeans and dark-skinned Africans.
researchers at Fudan University
genetically modified fish to detect oestrogen pollution in lakes and rivers, which is linked to male infertility.
, blood vessel development
, heart failure, and congenital heart disease
. 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. An approach that allows detailed study of the genetic controls of inflammation and the possibility of identifying potential new drugs.
Another focus of work is to understand how a gene called Hedgehog, a biological signal that underlies a number of human cancers, controls cell growth. This is fast becoming an avenue of research that is leading to new cancer therapies.
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 are delving into the complexities of muscle degeneration in genetic models of human musculoskeletal diseases, such as muscular dystrophy.
These studies exemplify how zebrafish research offers unique opportunities to understanding some of the greatest challenges in medical science, by enabling new discoveries of how cells and tissues work to be translated into new ways of understanding a broad range of human diseases.
Finally, and as demonstrated through ongoing research programmes, the zebrafish models affords an ideal opportunity, not only to identify novel candidates for genes underlying human disease, but offers a potential system in which to begin to develop novel therapeutic agents in drug discovery programmes, hence helping to identify new treatments.
grew a type of zebrafish adult stem cell
found in the eye
s of fish and mammals that develops into neuron
s in the retina
—the part of the eye that sends messages to the brain. These cell
s could be injected in the eye to treat diseases that damage retinal neurons—nearly every disease of the eye, including macular degeneration
, glaucoma
, and diabetes-related blindness
. Retinal damage is responsible for most cases of sight loss. 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 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 is working on the same approach in humans.
developed a new strain of zebrafish, named Casper, whose adult bodies were transparent. This allows for detailed visualization of cellular activity, circulation, metastasis
and many other phenomena. Because many gene functions are shared between fish and humans, Casper is expected to yield insight into human diseases such as leukemia and other cancers.
Freshwater fish
Freshwater fish are fish that spend some or all of their lives in freshwater, such as rivers and lakes, with a salinity of less than 0.05%. These environments differ from marine conditions in many ways, the most obvious being the difference in levels of salinity...
belonging to the minnow family
Family (biology)
In biological classification, family is* a taxonomic rank. Other well-known ranks are life, domain, kingdom, phylum, class, order, genus, and species, with family fitting between order and genus. As for the other well-known ranks, there is the option of an immediately lower rank, indicated by the...
(Cyprinidae) of order
Order (biology)
In scientific classification used in biology, the order is# a taxonomic rank used in the classification of organisms. Other well-known ranks are life, domain, kingdom, phylum, class, family, genus, and species, with order fitting in between class and family...
Cypriniformes
Cypriniformes
The Cypriniformes are an order of ray-finned fish, including the carps, minnows, loaches and relatives. This order contains 5-6 families, over 320 genera, and more than 3,250 species, with new species being described every few months or so, and new genera being recognized regularly...
. It is a popular aquarium fish
Aquarium
An aquarium is a vivarium consisting of at least one transparent side in which water-dwelling plants or animals are kept. Fishkeepers use aquaria to keep fish, invertebrates, amphibians, marine mammals, turtles, and aquatic plants...
, frequently sold under the trade name zebra danio, and is an important vertebrate model organism
Model organism
A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Model organisms are in vivo models and are widely used to...
in scientific research.
Taxonomy
The zebrafish are Cyprinidae with a derivedDerived
In phylogenetics, a derived trait is a trait that is present in an organism, but was absent in the last common ancestor of the group being considered. This may also refer to structures that are not present in an organism, but were present in its ancestors, i.e. traits that have undergone secondary...
member of the genus Danio
Danio
The Danio genus comprises many of the species of danionins familiar to aquarists. The common name "danio" is used for members of the genera Danio and Devario.-Taxonomy:...
. It has a sister group
Cladistics
Cladistics is a method of classifying species of organisms into groups called clades, which consist of an ancestor organism and all its descendants . For example, birds, dinosaurs, crocodiles, and all descendants of their most recent common ancestor form a clade...
relationship with Danio kyathit
Danio kyathit
Danio kyathit is a small, schooling species of fish in the family Cyprinidae, native to Myanmar. Described in 1998, it is closely related to the better known zebrafish or zebra danio, D. rerio.-Description:...
.
Zebrafish are closely related to the genus Devario
Devario
The genus Devario comprises some danionins familiar to aquarists. Generally, they are larger fish than species of the genus Danio, they have short barbels , and generally have deeper bodies than Danio species, with species having vertical or horizontal stripes present...
, as demonstrated by a phylogenetic tree
Phylogenetic tree
A phylogenetic tree or evolutionary tree is a branching diagram or "tree" showing the inferred evolutionary relationships among various biological species or other entities based upon similarities and differences in their physical and/or genetic characteristics...
of close species.
Distribution
The zebrafish is native to the streams of the southeastern HimalayanHimalayas
The Himalaya Range or Himalaya Mountains Sanskrit: Devanagari: हिमालय, literally "abode of snow"), usually called the Himalayas or Himalaya for short, is a mountain range in Asia, separating the Indian subcontinent from the Tibetan Plateau...
region, including the countries India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
, Pakistan
Pakistan
Pakistan , officially the Islamic Republic of Pakistan is a sovereign state in South Asia. It has a coastline along the Arabian Sea and the Gulf of Oman in the south and is bordered by Afghanistan and Iran in the west, India in the east and China in the far northeast. In the north, Tajikistan...
, Bangladesh
Bangladesh
Bangladesh , officially the People's Republic of Bangladesh is a sovereign state located in South Asia. It is bordered by India on all sides except for a small border with Burma to the far southeast and by the Bay of Bengal to the south...
, Nepal
Nepal
Nepal , officially the Federal Democratic Republic of Nepal, is a landlocked sovereign state located in South Asia. It is located in the Himalayas and bordered to the north by the People's Republic of China, and to the south, east, and west by the Republic of India...
, and Myanmar
Myanmar
Burma , officially the Republic of the Union of Myanmar , is a country in Southeast Asia. Burma is bordered by China on the northeast, Laos on the east, Thailand on the southeast, Bangladesh on the west, India on the northwest, the Bay of Bengal to the southwest, and the Andaman Sea on the south....
. It arose in the Ganges region in eastern India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
, and commonly inhabits streams, canals, ditches, ponds, and slow-moving to stagnant water bodies, including rice fields.
Zebrafish have been introduced
Introduced species
An introduced species — or neozoon, alien, exotic, non-indigenous, or non-native species, or simply an introduction, is a species living outside its indigenous or native distributional range, and has arrived in an ecosystem or plant community by human activity, either deliberate or accidental...
to parts of the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, presumably by deliberate release or by escape from fish farms. They have also been sighted in Colombia
Colombia
Colombia, officially the Republic of Colombia , is a unitary constitutional republic comprising thirty-two departments. The country is located in northwestern South America, bordered to the east by Venezuela and Brazil; to the south by Ecuador and Peru; to the north by the Caribbean Sea; to the...
.
Description
The fish is named for the five uniform, pigmented, horizontal blue stripes on the side of the body, all of which extend to the end of the caudal fin. Its shape is fusiform and laterally compressed, with its mouth directed upwards. Males are torpedoTorpedo
The modern torpedo is a self-propelled missile weapon with an explosive warhead, launched above or below the water surface, propelled underwater towards a target, and designed to detonate either on contact with it or in proximity to it.The term torpedo was originally employed for...
-shaped and have gold stripes between the blue stripes; females have a larger, whitish belly and have silver stripes instead of gold. Adult females will exhibit a small genital papilla in front of the anal fin origin. The zebrafish can grow to 6.4 centimetres (2.5 in), although it is uncommon for them to grow past 4 cm in captivity. Life-span in captivity is around 2–3 years, although in ideal conditions, may extend to 5 years.
Reproduction
The approximate generation time for the Danio is 3–4 months. A male must be present for ovulation and spawningSpawn (biology)
Spawn refers to the eggs and sperm released or deposited, usually into water, by aquatic animals. As a verb, spawn refers to the process of releasing the eggs and sperm, also called spawning...
to occur. Females are able to spawn at intervals of 2–3 days, laying hundreds of eggs in each clutch
Clutch (eggs)
A clutch of eggs refers to all the eggs produced by birds or reptiles, often at a single time, particularly those laid in a nest.In birds, destruction of a clutch by predators, , results in double-clutching...
. Upon release, embryonic development begins; absent 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
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
. Development progresses rapidly. Precursors to all major organs appear within 36 hours of fertilization, and hatching takes place 12-36 hours later, depending on the embryo's internal conditions and the external temperature, ideally 28.5 °C (83.3 °F). Swimming and feeding behavior begin about 36 hours later. The sex of juveniles cannot be distinguished except by dissection, and sex determinants are not clearly understood.
Feeding
The zebrafish is omnivorous. It primarily eats zooplanktonZooplankton
Zooplankton are heterotrophic plankton. Plankton are organisms drifting in oceans, seas, and bodies of fresh water. The word "zooplankton" is derived from the Greek zoon , meaning "animal", and , meaning "wanderer" or "drifter"...
, insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...
s, insect larva
Larva
A larva is a distinct juvenile form many animals undergo before metamorphosis into adults. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle...
e, and phytoplankton
Phytoplankton
Phytoplankton are the autotrophic component of the plankton community. The name comes from the Greek words φυτόν , meaning "plant", and πλαγκτός , meaning "wanderer" or "drifter". Most phytoplankton are too small to be individually seen with the unaided eye...
. It can eat a variety of other foods, such as worm
Worm
The term worm refers to an obsolete taxon used by Carolus Linnaeus and Jean-Baptiste Lamarck for all non-arthropod invertebrate animals, and stems from the Old English word wyrm. Currently it is used to describe many different distantly-related animals that typically have a long cylindrical...
s and small crustacean
Crustacean
Crustaceans form a very large group of arthropods, usually treated as a subphylum, which includes such familiar animals as crabs, lobsters, crayfish, shrimp, krill and barnacles. The 50,000 described species range in size from Stygotantulus stocki at , to the Japanese spider crab with a leg span...
s if its preferred sources are not readily available. Most danios accept common food flakes and tubifex worms in the aquarium
Aquarium
An aquarium is a vivarium consisting of at least one transparent side in which water-dwelling plants or animals are kept. Fishkeepers use aquaria to keep fish, invertebrates, amphibians, marine mammals, turtles, and aquatic plants...
.
Strains
Recently, transgenic zebrafish have become commercially available that express greenGreen fluorescent protein
The green fluorescent protein is a protein composed of 238 amino acid residues that exhibits bright green fluorescence when exposed to blue light. Although many other marine organisms have similar green fluorescent proteins, GFP traditionally refers to the protein first isolated from the...
, red, and yellow fluorescent protein
Yellow fluorescent protein
Yellow Fluorescent Protein is a genetic mutant of green fluorescent protein, derived from Aequorea victoria. Its excitation peak is 514nm and its emission peak is 527nm....
s. They are tradenamed GloFish
GloFish
The GloFish is a patented and trademarked brand of genetically modified fluorescent zebrafish with bright red, green, orange-yellow, blue, and purple fluorescent colors...
; other cultivated varieties include 'golden', 'sandy', 'longfin' and 'leopard'.
The leopard danio, previously known as Danio frankei, is a spotted colour morph of the zebrafish caused by a pigment mutation. Xanthistic
Xanthochromism
Xanthochromism is a term that may be applied to birds, fish and other animals whose colouration is unusually yellow through an excess of yellow pigment, or possibly a loss of darker pigments that allows yellow pigment to be unusually dominant...
forms of both the zebra
Zebra
Zebras are several species of African equids united by their distinctive black and white stripes. Their stripes come in different patterns unique to each individual. They are generally social animals that live in small harems to large herds...
and leopard
Leopard
The leopard , Panthera pardus, is a member of the Felidae family and the smallest of the four "big cats" in the genus Panthera, the other three being the tiger, lion, and jaguar. The leopard was once distributed across eastern and southern Asia and Africa, from Siberia to South Africa, but its...
pattern, along with long-finned subspecies, have been obtained via selective breeding programs for the aquarium trade.
Wild-type strains
The Zebra Fish Information Network provides up-to-date information about current known wild-type (WT) strains of D. rerio. The most commonly found WT strains are: AB, TÜ, IN and WIK.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.Aquarium care
Zebrafish are hardy fish and considered good for beginner aquaristsAquarium
An aquarium is a vivarium consisting of at least one transparent side in which water-dwelling plants or animals are kept. Fishkeepers use aquaria to keep fish, invertebrates, amphibians, marine mammals, turtles, and aquatic plants...
. Their decades of popularity can also be attributed to their playful disposition, as well as their rapid breeding, beauty, price, and broad availability. They thrive best in 22–28 °C (71.6–82.4 F) water. They need an aquarium of 10 gallons (37.9 l) or more, and they do well in schools. They also thrive as shoals
Shoaling and schooling
In biology, any group of fish that stay together for social reasons are said to be shoaling , and if, in addition, the group is swimming in the same direction in a coordinated manner, they are said to be schooling . In common usage, the terms are sometimes used rather loosely...
of six or more, and interact well with other fish types in the aquarium. However, they are susceptible to Oodinium
Oodinium
Oödinium is a genus of microscopic parasitic dinoflagellates. They live off salt and fresh water fish, causing a type of fish velvet disease . One species has also been recorded on various cnidarians .The host typically develops small yellow or gold dust scattered on its head, fins and body...
or velvet disease, microsporidia
Microsporidia
The microsporidia constitute a phylum of spore-forming unicellular parasites. They were once thought to be protists but are now known to be fungi. Loosely 1500 of the probably more than one million species are named now. Microsporidia are restricted to animal hosts, and all major groups of animals...
(Pseudoloma neurophilia), and Mycobacterium
Mycobacterium
Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. The genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy...
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 scientific research
Model organism
A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Model organisms are in vivo models and are widely used to...
for studies of vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
development and gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
function. George Streisinger
George Streisinger
George Streisinger was a molecular biologist at the University of Oregon. He was the first person to clone a vertebrate, cloning zebra fish in his University of Oregon laboratory. He also pioneered work in the genetics of the T-even bacterial viruses...
at the University of Oregon
University of Oregon
-Colleges and schools:The University of Oregon is organized into eight schools and colleges—six professional schools and colleges, an Arts and Sciences College and an Honors College.- School of Architecture and Allied Arts :...
established its utility. Success with it in large scale forward genetic screen
Genetic screen
A genetic screen is a procedure or test to identify and select individuals who possess a phenotype of interest. A genetic screen for new genes is often referred to as forward genetics as opposed to reverse genetics, the term for identifying mutant alleles in genes that are already known...
s (commonly referred to as the Tübingen/Boston screens) consolidated its importance. The scholarly journal Development devoted an issue to research using it in celebration of this landmark. It has a dedicated online database of genetic, genomic, and developmental information, the Zebrafish Information Network
Zebrafish Information Network
The Zebrafish Information Network is an online biological database of information about the zebrafish . The zebrafish is a widely used model organism for genetic, genomic, and developmental studies, and ZFIN provides an integrated interface for querying and displaying the large volume of data...
(ZFIN). D. rerio is one of the few fish species to have reached space
Animals in space
Animals in space originally only served to test the survivability of spaceflight, before manned space missions were attempted. Later, animals were also flown to investigate various biological processes and the effects microgravity and space flight might have on them...
. They may supplement higher vertebrate models, such as rats and mice.
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
, oncology
Oncology
Oncology is a branch of medicine that deals with cancer...
, toxicology
Toxicology
Toxicology is a branch of biology, chemistry, and medicine concerned with the study of the adverse effects of chemicals on living organisms...
, reproductive studies, teratology
Teratology
Teratology is the study of abnormalities of physiological development. It is often thought of as the study of human birth defects, but it is much broader than that, taking in other non-birth developmental stages, including puberty; and other non-human life forms, including plants.- Etymology :The...
, genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
, neurobiology, environmental science
Environmental science
Environmental science is an interdisciplinary academic field that integrates physical and biological sciences, to the study of the environment, and the solution of environmental problems...
s, stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
and regenerative medicine
Regenerative medicine
Regenerative medicine is the "process of replacing or regenerating human cells, tissues or organs to restore orestablish normal function". This field holds the promise of regenerating damaged tissues and organs in the body by replacing damaged tissue and/or by stimulating the body's own repair...
, and evolutionary theory.
Attractive characteristics
Its greatest advantages for use as a model system include:- Fully sequenced genome
- Well-understood, easily observable and testable developmental behaviors
- Availability of well-characterized mutants
Other advantages:
- Rapid embryonic developmentEmbryogenesisEmbryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...
(progressing from eggs to larvae in under three days, although overall generation time is comparable to that of mice) - Large, robust, and transparent embryos that develop outside the mother
- Nearly constant size during early development facilitates simple staining techniques
- Drugs may be administered by adding directly to the tank.
- Unfertilized eggs can be made to divide
- Two-celled embryo can be fused into a single cell, creating a homozygous embryo
- Demonstrated similarity to mammalian models and humans in toxicity testing
- Exhibits a diurnal sleep cycle with similarities to mammalian sleep behavior and physiology
Regeneration
Zebrafish have the ability to regenerateRegeneration (biology)
In biology, regeneration is the process of renewal, restoration, and growth that makes genomes, cells, organs, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. At its most...
fins, skin, the heart and the brain (in larval stages). Heart muscle regeneration does not make use of stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s; instead, mature heart muscle cells regress to a stem-cell-like state and redifferentiate. In 2011, the British Heart Foundation
British Heart Foundation
The British Heart Foundation is a charity organisation in Britain that funds research, education, care and awareness campaigns aimed to prevent heart diseases in humans.-Foundation:...
ran an advertising campaign (including on television and on line) publicising their intention to study the applicability of this ability to humans by "spend[ing] £50 million on a programme of groundbreaking research that could help us begin to repair damaged [human] hearts."
Zebrafish have also been found to regenerate photoreceptor cells and retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
l neurons following injury. The mechanisms of this regeneration are unknown. Researchers frequently amputate the dorsal and ventral tail fins and analyze their regrowth to test for mutations. This research is leading the scientific community in the understanding of healing/repair mechanisms in vertebrates. It has also been found if the same fin is damaged enough times, the fish will grow a new fin which will have mutated only a small amount. Most scientists believe this is a defence mechanism to try to prevent the fin from being damaged again.
Gene expression
A common reverse geneticsReverse genetics
Reverse genetics is an approach to discovering the function of a gene by analyzing the phenotypic effects of specific gene sequences obtained by DNA sequencing. This investigative process proceeds in the opposite direction of so-called forward genetic screens of classical genetics...
technique is to reduce gene expression
Gene knockdown
Gene knockdown refers to techniques by which the expression of one or more of an organism's genes is reduced, either through genetic modification or by treatment with a reagent such as a short DNA or RNA oligonucleotide with a sequence complementary to either an mRNA transcript or a gene...
or modify splicing
Splicing (genetics)
In molecular biology and genetics, splicing is a modification of an RNA after transcription, in which introns are removed and exons are joined. This is needed for the typical eukaryotic messenger RNA before it can be used to produce a correct protein through translation...
using Morpholino
Morpholino
In molecular biology, a Morpholino is a molecule in a particular structural family that is used to modify gene expression. Morpholino oligomers are an antisense technology used to block access of other molecules to specific sequences within nucleic acid...
antisense technology. Morpholino oligonucleotide
Oligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...
s (MO) are stable, synthetic macromolecules that contain the same bases as DNA or RNA; by binding to complementary RNA sequences, they reduce the expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of specific genes. The journal Genesis devoted an issue to research using MO, mostly in D. rerio. 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. 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 one of the two gene paralogs reliably due to complementation
Complementation (genetics)
In genetics, complementation refers to a relationship between two different strains of an organism which both have homozygous recessive mutations that produce the same phenotype . These strains are true breeding for their mutation...
by the other paralog.
Despite the complications of the zebrafish genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
, a number of commercially available global platforms for analysis of both gene expression by microarrays
Expression profiling
In the field of molecular biology, gene expression profiling is the measurement of the activity of thousands of genes at once, to create a global picture of cellular function. These profiles can, for example, distinguish between cells that are actively dividing, or show how the cells react to a...
and promoter regulation using ChIP-on-chip
ChIP-on-chip
ChIP-on-chip is a technique that combines chromatin immunoprecipitation with microarray technology . Like regular ChIP, ChIP-on-chip is used to investigate interactions between proteins and DNA in vivo...
exist.
Gene sequencing
In 2009, researchers at the Institute of Genomics and Integrative BiologyInstitute of Genomics and Integrative Biology
Institute of Genomics and Integrative Biology is a scientific research institute devoted primarily to integrated biological research. It is a part of Council of Scientific and Industrial Research , India....
, Delhi
Delhi
Delhi , officially National Capital Territory of Delhi , is the largest metropolis by area and the second-largest by population in India, next to Mumbai. It is the eighth largest metropolis in the world by population with 16,753,265 inhabitants in the Territory at the 2011 Census...
announced the sequencing of a wild caught strain, containing 1.7 billion
genetic letters.
Mitochondrial DNA
In October 2001, researchers from the University of OklahomaUniversity of Oklahoma
The University of Oklahoma is a coeducational public research university located in Norman, Oklahoma. Founded in 1890, it existed in Oklahoma Territory near Indian Territory for 17 years before the two became the state of Oklahoma. the university had 29,931 students enrolled, most located at its...
published D. rerio's complete mitochondrial DNA
Mitochondrial DNA
Mitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...
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
Goldfish
The goldfish is a freshwater fish in the family Cyprinidae of order Cypriniformes. It was one of the earliest fish to be domesticated, and is one of the most commonly kept aquarium fish....
(Carassius auratus) and 21 longer than the carp
Carp
Carp are various species of oily freshwater fish of the family Cyprinidae, a very large group of fish native to Europe and Asia. The cypriniformes are traditionally grouped with the Characiformes, Siluriformes and Gymnotiformes to create the superorder Ostariophysi, since these groups have certain...
(Cyprinus carpio). Its gene order and content are identical to the common vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
form of mitochondrial DNA. It contains 13 protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
-coding genes and a noncoding control region containing the origin of replication
Origin of replication
The origin of replication is a particular sequence in a genome at which replication is initiated. This can either be DNA replication in living organisms such as prokaryotes and eukaryotes, or RNA replication in RNA viruses, such as double-stranded RNA viruses...
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
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
sequences.
Pigmentation gene
In December 2005, a study of the golden strain identified the gene responsible for its unusual pigmentation as SLC24A5SLC24A5
Sodium/potassium/calcium exchanger 5 also known as solute carrier family 24 member 5 is a protein that in humans is encoded by the SLC24A5 gene that has a major influence on natural skin colour variation. The NCKX5 protein is a member of the potassium-dependent sodium/calcium exchanger family...
, a solute
Solution
In chemistry, a solution is a homogeneous mixture composed of only one phase. In such a mixture, a solute is dissolved in another substance, known as a solvent. The solvent does the dissolving.- Types of solutions :...
carrier that appeared to be required for melanin
Melanin
Melanin is a pigment that is ubiquitous in nature, being found in most organisms . In animals melanin pigments are derivatives of the amino acid tyrosine. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms...
production, and confirmed its function with a Morpholino knockdown. The orthologous gene was then characterized in humans and a one base pair difference was found to strongly segregate fair-skinned Europeans and dark-skinned Africans.
Transgenesis
Transgenesis 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.Oestrogen detection
In January 2007, ChineseChina
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
researchers at Fudan University
Fudan University
Fudan University , located in Shanghai, is one of the oldest and most selective universities in China, and is a member of the C9 League. Its institutional predecessor was founded in 1905, shortly before the end of China's imperial Qing dynasty...
genetically modified fish to detect oestrogen pollution in lakes and rivers, which is linked to male infertility.
In medical research
In cardiovascular research the zebrafish is being used to model blood clottingCoagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
, blood vessel development
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
, heart failure, and congenital heart disease
Congenital heart defect
A congenital heart defect is a defect in the structure of the heart and great vessels which is present at birth. Many types of heart defects exist, most of which either obstruct blood flow in the heart or vessels near it, or cause blood to flow through the heart in an abnormal pattern. Other...
. In programmes of research into acute inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, a major underpinning process in many diseases, researchers have established a zebrafish model of inflammation, and its resolution. An approach that allows detailed study of the genetic controls of inflammation and the possibility of identifying potential new drugs.
Another focus of work is to understand how a gene called Hedgehog, a biological signal that underlies a number of human cancers, controls cell growth. This is fast becoming an avenue of research that is leading to new cancer therapies.
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 are delving into the complexities of muscle degeneration in genetic models of human musculoskeletal diseases, such as muscular dystrophy.
These studies exemplify how zebrafish research offers unique opportunities to understanding some of the greatest challenges in medical science, by enabling new discoveries of how cells and tissues work to be translated into new ways of understanding a broad range of human diseases.
Finally, and as demonstrated through ongoing research programmes, the zebrafish models affords an ideal opportunity, not only to identify novel candidates for genes underlying human disease, but offers a potential system in which to begin to develop novel therapeutic agents in drug discovery programmes, hence helping to identify new treatments.
Repairing retinal damage
In 2007, researchers at University College LondonUniversity College London
University College London is a public research university located in London, United Kingdom and the oldest and largest constituent college of the federal University of London...
grew a type of zebrafish adult stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
found in the eye
Eye
Eyes are organs that detect light and convert it into electro-chemical impulses in neurons. The simplest photoreceptors in conscious vision connect light to movement...
s of fish and mammals that develops into neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s in the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
—the part of the eye that sends messages to the brain. These cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s could be injected in the eye to treat diseases that damage retinal neurons—nearly every disease of the eye, including macular degeneration
Macular degeneration
Age-related macular degeneration is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults...
, glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
, and diabetes-related blindness
Blindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...
. Retinal damage is responsible for most cases of sight loss. 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 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 is working on the same approach in humans.
Transparent adult bodies
In 2008, researchers at Children's Hospital BostonChildren's Hospital Boston
Children's Hospital Boston is a 396-licensed bed children's hospital in the Longwood Medical and Academic Area of Boston, Massachusetts.At 300 Longwood Avenue, Children's is adjacent both to its teaching affiliate, Harvard Medical School, and to Dana-Farber Cancer Institute...
developed a new strain of zebrafish, named Casper, whose adult bodies were transparent. This allows for detailed visualization of cellular activity, circulation, metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
and many other phenomena. Because many gene functions are shared between fish and humans, Casper is expected to yield insight into human diseases such as leukemia and other cancers.
See also
- The subfamily DanioninaeDanioninThe danionins are a group of small minnow-type fish belonging to the family Cyprinidae. Members of this group are mostly in the genera Danio and Devario. They are native to the fresh waters of southeast Asia. Many species are brightly coloured and are available as aquarium fish worldwide...
- Development of fish: post-fertilization development and axes formation Regional specification#Fish
- List of freshwater aquarium fish species
- See-through frog
- GloFishGloFishThe GloFish is a patented and trademarked brand of genetically modified fluorescent zebrafish with bright red, green, orange-yellow, blue, and purple fluorescent colors...
External links
- The Zebrafish Information Network (ZFIN)
- The Zebrafish International Resource Center (ZIRC)
- The Zebrafish Genome Sequencing Project (Wellcome Trust Sanger Institute)
- FishMap : The Zebrafish Community Genomics Browser
- Zebrafish GenomeWiki Beta Preview maintained at the Institute of Genomics and Integrative BiologyInstitute of Genomics and Integrative BiologyInstitute of Genomics and Integrative Biology is a scientific research institute devoted primarily to integrated biological research. It is a part of Council of Scientific and Industrial Research , India....
- The Zebrafish wild-type strain Genome sequencing initiative at the Institute of Genomics and Integrative BiologyInstitute of Genomics and Integrative BiologyInstitute of Genomics and Integrative Biology is a scientific research institute devoted primarily to integrated biological research. It is a part of Council of Scientific and Industrial Research , India....
- Danio rerio
- Danio rerio embryonic development images
- Sanger Institute Zebrafish Mutation Resource
- Heartbeat and blood flow in transgenic Zebrafish - movies
- FishforScience.com - Using zebrafish for medical research.