Editing Zebrafish (section)

==Medical research==

===Cancer===
Zebrafish have been used to make several transgenic models of cancer, including [[melanoma]], [[leukemia]], [[pancreatic cancer]] and [[hepatocellular carcinoma]].<ref>{{cite journal |vauthors=Liu S, Leach SD |title=Zebrafish models for cancer |journal=[[Annual Review of Pathology]] |volume=6 |pages=71–93 |year=2011 |pmid=21261518 |doi=10.1146/annurev-pathol-011110-130330}}</ref><ref>{{cite web |url=https://www.sciencedaily.com/releases/2011/03/110323141852.htm |title=Zebrafish model of human melanoma reveals new cancer gene |website=[[Science Daily]] |date=March 23, 2011 |access-date=April 28, 2014 |archive-date=May 19, 2024 |archive-url=https://web.archive.org/web/20240519141132/https://www.sciencedaily.com/releases/2011/03/110323141852.htm |url-status=live}}</ref> Zebrafish expressing mutated forms of either the BRAF or NRAS [[oncogene]]s develop melanoma when placed onto a p53 deficient background. [[Histology|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.<ref>{{cite journal |vauthors=Ceol CJ, Houvras Y, Jane-Valbuena J, Bilodeau S, Orlando DA, Battisti V, Fritsch L, Lin WM, Hollmann TJ, Ferré F, Bourque C, Burke CJ, Turner L, Uong A, Johnson LA, Beroukhim R, Mermel CH, Loda M, Ait-Si-Ali S, Garraway LA, Young RA, Zon LI |display-authors=6 |title=The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset |journal=[[Nature (journal)|Nature]] |volume=471 |issue=7339 |pages=513–517 |date=March 2011 |pmid=21430779 |pmc=3348545 |doi=10.1038/nature09806 |bibcode=2011Natur.471..513C}}</ref> 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.<ref>{{cite journal |vauthors=White RM, Cech J, Ratanasirintrawoot S, Lin CY, Rahl PB, Burke CJ, Langdon E, Tomlinson ML, Mosher J, Kaufman C, Chen F, Long HK, Kramer M, Datta S, Neuberg D, Granter S, Young RA, Morrison S, Wheeler GN, Zon LI |display-authors=6 |title=DHODH modulates transcriptional elongation in the neural crest and melanoma |journal=[[Nature (journal)|Nature]] |volume=471 |issue=7339 |pages=518–522 |date=March 2011 |pmid=21430780 |pmc=3759979 |doi=10.1038/nature09882 |bibcode=2011Natur.471..518W}}</ref> 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.<ref>{{cite news |url=https://www.sciencedaily.com/releases/2011/03/110323141838.htm |title=Arthritis Drug Could Help Beat Melanoma Skin Cancer, Study Finds |newspaper=Sciencedaily |date=March 24, 2011 |access-date=November 15, 2012 |archive-date=May 19, 2024 |archive-url=https://web.archive.org/web/20240519141108/https://www.sciencedaily.com/releases/2011/03/110323141838.htm |url-status=live}}</ref>

===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.<ref>{{cite journal |doi=10.1186/1471-213X-11-21 |pmid=21473762 |pmc=3078894 |title=The zebrafish heart regenerates after cryoinjury-induced myocardial infarction |year=2011 |last1=Chablais |first1=Fabian |last2=Veit |first2=Julia |last3=Rainer |first3=Gregor |last4=Jaźwińska |first4=Anna |journal=[[BMC Developmental Biology]] |volume=11 |page=21 |doi-access=free}}</ref> The [[Alpha-1 adrenergic receptor|Alpha-1 adrenergic signalling]] mechanism involved in this process was identified in a 2023 study.<ref>{{Cite journal |last1=Apaydin |first1=Onur |last2=Altaikyzy |first2=Akerke |last3=Filosa |first3=Alessandro |last4=Sawamiphak |first4=Suphansa |date=2023-11-20 |title=Alpha-1 adrenergic signaling drives cardiac regeneration via extracellular matrix remodeling transcriptional program in zebrafish macrophages |journal=[[Developmental Cell]] |volume=58 |issue=22 |pages=2460–2476.e7 |doi=10.1016/j.devcel.2023.09.011 |pmid=37875117 |s2cid=264449103 |issn=1534-5807 |doi-access=free}}</ref> Zebrafish is also used as a model for [[Coagulation|blood clotting]], [[Angiogenesis|blood vessel development]], and [[congenital heart defect|congenital heart and kidney disease]].<ref>{{cite journal |vauthors=Drummond IA |title=Kidney development and disease in the zebrafish |journal=[[Journal of the American Society of Nephrology]] |volume=16 |issue=2 |pages=299–304 |date=February 2005 |pmid=15647335 |doi=10.1681/ASN.2004090754 |s2cid=25428361 |doi-access=}}</ref>

===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.<ref>{{cite web |url=http://www.fishforscience.com/disease/inflammatory-disease |title=Investigating inflammatory disease using zebrafish |publisher=Fish For Science |access-date=November 15, 2012 |archive-date=January 9, 2013 |archive-url=https://web.archive.org/web/20130109005739/http://www.fishforscience.com/disease/inflammatory-disease}}</ref>

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)<ref>{{cite journal |vauthors=Le Guyader D, Redd MJ, Colucci-Guyon E, Murayama E, Kissa K, Briolat V, Mordelet E, Zapata A, Shinomiya H, Herbomel P |display-authors=6 |title=Origins and unconventional behavior of neutrophils in developing zebrafish |journal=Blood |volume=111 |issue=1 |pages=132–141 |date=January 2008 |pmid=17875807 |doi=10.1182/blood-2007-06-095398 |s2cid=8853409 |doi-access=free}}</ref> while adaptive immunity is not functionally mature until at least 4 weeks postfertilization.<ref>{{Cite book |title=Current Topics in Innate Immunity II |volume=946 |last1=Novoa |first1=Beatriz |last2=Figueras |first2=Antonio |chapter=Zebrafish: Model for the Study of Inflammation and the Innate Immune Response to Infectious Diseases |name-list-style=vanc |date=2012-01-01 |publisher=Springer New York |isbn=978-1-4614-0105-6 |editor-last=Lambris |editor-first=John D. |series=[[Advances in Experimental Medicine and Biology]] |pages=253–275 |language=en |doi=10.1007/978-1-4614-0106-3_15 |pmid=21948373 |editor-last2=Hajishengallis |editor-first2=George |hdl=10261/44975 |s2cid=6914876}}</ref>

===Infectious diseases===
As the immune system is relatively conserved between zebrafish and humans, many human infectious diseases can be modeled in zebrafish.<ref>{{cite journal |vauthors=Meeker ND, Trede NS |title=Immunology and zebrafish: spawning new models of human disease |journal=[[Developmental and Comparative Immunology]] |volume=32 |issue=7 |pages=745–757 |year=2008 |pmid=18222541 |doi=10.1016/j.dci.2007.11.011}}</ref><ref>{{cite journal |vauthors=Renshaw SA, Trede NS |title=A model 450 million years in the making: zebrafish and vertebrate immunity |journal=Disease Models & Mechanisms |volume=5 |issue=1 |pages=38–47 |date=January 2012 |pmid=22228790 |pmc=3255542 |doi=10.1242/dmm.007138}}</ref><ref>{{cite journal |vauthors=Meijer AH, Spaink HP |title=Host-pathogen interactions made transparent with the zebrafish model |journal=Current Drug Targets |volume=12 |issue=7 |pages=1000–1017 |date=June 2011 |pmid=21366518 |pmc=3319919 |doi=10.2174/138945011795677809}}</ref><ref>{{cite journal |vauthors=van der Vaart M, Spaink HP, Meijer AH |title=Pathogen recognition and activation of the innate immune response in zebrafish |journal=[[Advances in Hematology]] |volume=2012 |page=159807 |year=2012 |pmid=22811714 |pmc=3395205 |doi=10.1155/2012/159807 |doi-access=free}}</ref> The transparent early life stages are well suited for ''in vivo'' imaging and genetic dissection of host-pathogen interactions.<ref>{{cite journal |vauthors=Benard EL, van der Sar AM, Ellett F, Lieschke GJ, Spaink HP, Meijer AH |title=Infection of zebrafish embryos with intracellular bacterial pathogens |journal=[[Journal of Visualized Experiments]] |issue=61 |date=March 2012 |pmid=22453760 |pmc=3415172 |doi=10.3791/3781}}</ref><ref>{{cite journal |vauthors=Meijer AH, van der Vaart M, Spaink HP |title=Real-time imaging and genetic dissection of host-microbe interactions in zebrafish |journal=Cellular Microbiology |volume=16 |issue=1 |pages=39–49 |date=January 2014 |pmid=24188444 |doi=10.1111/cmi.12236 |doi-access=free|hdl=1887/3736301 |hdl-access=free}}</ref><ref>{{cite journal |vauthors=Torraca V, Masud S, Spaink HP, Meijer AH |title=Macrophage-pathogen interactions in infectious diseases: new therapeutic insights from the zebrafish host model |journal=Disease Models & Mechanisms |volume=7 |issue=7 |pages=785–797 |date=July 2014 |pmid=24973749 |pmc=4073269 |doi=10.1242/dmm.015594}}</ref><ref>{{cite journal |vauthors=Levraud JP, Palha N, Langevin C, Boudinot P |title=Through the looking glass: witnessing host-virus interplay in zebrafish |journal=[[Trends in Microbiology]] |volume=22 |issue=9 |pages=490–497 |date=September 2014 |pmid=24865811 |doi=10.1016/j.tim.2014.04.014}}</ref> 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.<ref>{{Cite book |vauthors=Ramakrishnan L |chapter=Looking within the Zebrafish to Understand the Tuberculous Granuloma |volume=783 |pages=251–66 |year=2013 |pmid=23468113 |doi=10.1007/978-1-4614-6111-1_13 |isbn=978-1-4614-6110-4 |series=Advances in Experimental Medicine and Biology |title=The New Paradigm of Immunity to Tuberculosis}}</ref><ref>{{cite journal |vauthors=Ramakrishnan L |title=The zebrafish guide to tuberculosis immunity and treatment |journal=Cold Spring Harbor Symposia on Quantitative Biology |volume=78 |pages=179–192 |year=2013 |pmid=24643219 |doi=10.1101/sqb.2013.78.023283 |doi-access=free}}</ref><ref>{{cite journal |vauthors=Cronan MR, Tobin DM |title=Fit for consumption: zebrafish as a model for tuberculosis |journal=Disease Models & Mechanisms |volume=7 |issue=7 |pages=777–784 |date=July 2014 |pmid=24973748 |pmc=4073268 |doi=10.1242/dmm.016089}}</ref><ref>{{cite journal |vauthors=Meijer AH |title=Protection and pathology in TB: learning from the zebrafish model |journal=Seminars in Immunopathology |volume=38 |issue=2 |pages=261–273 |date=March 2016 |pmid=26324465 |pmc=4779130 |doi=10.1007/s00281-015-0522-4}}</ref> Other bacteria commonly studied using zebrafish models include ''Clostridioides difficile'', ''Staphylococcus aureus'', and ''Pseudomonas aeruginosa''.<ref>{{Cite journal |last1=Franza |first1=Maria |last2=Varricchio |first2=Romualdo |last3=Alloisio |first3=Giulia |last4=De Simone |first4=Giovanna |last5=Di Bella |first5=Stefano |last6=Ascenzi |first6=Paolo |last7=di Masi |first7=Alessandra |date=2024-11-08 |title=Zebrafish (Danio rerio) as a Model System to Investigate the Role of the Innate Immune Response in Human Infectious Diseases |journal=[[International Journal of Molecular Sciences]] |language=en |volume=25 |issue=22 |page=12008 |doi=10.3390/ijms252212008 |doi-access=free |pmid=39596075 |issn=1422-0067 |pmc=11593600}}</ref> Furthermore, robotic technology has been developed for high-throughput antimicrobial drug screening using zebrafish infection models.<ref>{{cite journal |vauthors=Spaink HP, Cui C, Wiweger MI, Jansen HJ, Veneman WJ, Marín-Juez R, de Sonneville J, Ordas A, Torraca V, van der Ent W, Leenders WP, Meijer AH, Snaar-Jagalska BE, Dirks RP |display-authors=6 |title=Robotic injection of zebrafish embryos for high-throughput screening in disease models |journal=Methods |volume=62 |issue=3 |pages=246–254 |date=August 2013 |pmid=23769806 |doi=10.1016/j.ymeth.2013.06.002 |doi-access=free |hdl=10044/1/53161 |hdl-access=free}}</ref><ref>{{cite journal |vauthors=Veneman WJ, Marín-Juez R, de Sonneville J, Ordas A, Jong-Raadsen S, Meijer AH, Spaink HP |title=Establishment and optimization of a high throughput setup to study Staphylococcus epidermidis and Mycobacterium marinum infection as a model for drug discovery |journal=[[Journal of Visualized Experiments]] |volume=88 |issue=88 |pages=e51649 |date=June 2014 |pmid=24998295 |pmc=4206090 |doi=10.3791/51649}}</ref>

===Repairing retinal damage===
[[File:Development of the retina.tif|thumb|400px|The development of a single zebrafish retina captured on a light sheet microscope approx. every 12 hours from 1.5 days to 3.5 days after birth of the embryo]]
Another notable characteristic of the zebrafish is that it possesses four types of [[cone cell]], 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.<ref>{{cite journal |vauthors=Allison WT, Barthel LK, Skebo KM, Takechi M, Kawamura S, Raymond PA |title=Ontogeny of cone photoreceptor mosaics in zebrafish |journal=The Journal of Comparative Neurology |volume=518 |issue=20 |pages=4182–4195 |date=October 2010 |pmid=20878782 |pmc=3376642 |doi=10.1002/cne.22447}}</ref>

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]] found in the eyes of fish and mammals that develops into [[neuron]]s 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.<ref>{{cite journal |vauthors=Lawrence JM, Singhal S, Bhatia B, Keegan DJ, Reh TA, Luthert PJ, Khaw PT, Limb GA |display-authors=6 |title=MIO-M1 cells and similar muller glial cell lines derived from adult human retina exhibit neural stem cell characteristics |journal=Stem Cells |volume=25 |issue=8 |pages=2033–2043 |date=August 2007 |pmid=17525239 |doi=10.1634/stemcells.2006-0724 |doi-access=free}}</ref><ref>{{cite news |url=http://www.chinapost.com.tw/health/eye%20health/2007/08/03/116860/Zebra-fish.htm |title=Zebra fish may point way to cure for blindness |author=<!--Staff writer(s); no by-line.--> |date=August 3, 2007 |newspaper=[[The China Post]] |archive-url=https://web.archive.org/web/20120910131642/http://www.chinapost.com.tw/health/eye%20health/2007/08/03/116860/Zebra-fish.htm |archive-date=2012-09-10}}</ref>

=== Muscular dystrophies ===
[[Muscular dystrophy|Muscular dystrophies]] (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.<ref name="Model organisms in the fight agains"/> For example, the ''sapje'' (''sap'') mutant is the zebrafish orthologue of human [[Duchenne muscular dystrophy]] (DMD).<ref>{{cite journal |vauthors=Kunkel LM, Bachrach E, Bennett RR, Guyon J, Steffen L |title=Diagnosis and cell-based therapy for Duchenne muscular dystrophy in humans, mice, and zebrafish |language=En |journal=[[Journal of Human Genetics]] |volume=51 |issue=5 |pages=397–406 |date=May 2006 |pmid=16583129 |pmc=3518425 |doi=10.1007/s10038-006-0374-9}}</ref> The Machuca-Tzili and co-workers applied zebrafish to determine the role of alternative splicing factor, MBNL, in [[Myotonic dystrophy|myotonic dystrophy type 1]] (DM1) pathogenesis.<ref>{{cite journal |vauthors=Machuca-Tzili LE, Buxton S, Thorpe A, Timson CM, Wigmore P, Luther PK, Brook JD |title=Zebrafish deficient for Muscleblind-like 2 exhibit features of myotonic dystrophy |journal=Disease Models & Mechanisms |volume=4 |issue=3 |pages=381–392 |date=May 2011 |pmid=21303839 |pmc=3097459 |doi=10.1242/dmm.004150}}</ref> 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.<ref>{{cite journal |vauthors=Todd PK, Ackall FY, Hur J, Sharma K, Paulson HL, Dowling JJ |title=Transcriptional changes and developmental abnormalities in a zebrafish model of myotonic dystrophy type 1 |journal=Disease Models & Mechanisms |volume=7 |issue=1 |pages=143–155 |date=January 2014 |pmid=24092878 |pmc=3882056 |doi=10.1242/dmm.012427}}</ref> 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.<ref>{{cite journal |vauthors=Jones KJ, Morgan G, Johnston H, Tobias V, Ouvrier RA, Wilkinson I, North KN |title=The expanding phenotype of laminin alpha2 chain (merosin) abnormalities: case series and review |journal=Journal of Medical Genetics |volume=38 |issue=10 |pages=649–657 |date=October 2001 |pmid=11584042 |pmc=1734735 |doi=10.1136/jmg.38.10.649}}</ref> 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.<ref>{{cite journal |vauthors=Maves L |title=Recent advances using zebrafish animal models for muscle disease drug discovery |journal=Expert Opinion on Drug Discovery |volume=9 |issue=9 |pages=1033–1045 |date=September 2014 |pmid=24931439 |pmc=4697731 |doi=10.1517/17460441.2014.927435}}</ref>

=== 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.<ref>{{cite journal |vauthors=Witten PE, Hansen A, Hall BK |title=Features of mono- and multinucleated bone resorbing cells of the zebrafish Danio rerio and their contribution to skeletal development, remodeling, and growth |journal=Journal of Morphology |volume=250 |issue=3 |pages=197–207 |date=December 2001 |pmid=11746460 |doi=10.1002/jmor.1065 |s2cid=33403358}}</ref><ref>{{cite journal |vauthors=Carnovali M, Banfi G, Mariotti M |title=Zebrafish Models of Human Skeletal Disorders: Embryo and Adult Swimming Together |journal=BioMed Research International |volume=2019 |page=1253710 |year=2019 |pmid=31828085 |pmc=6886339 |doi=10.1155/2019/1253710 |doi-access=free}}</ref> 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]] and [[osteogenesis imperfecta]].<ref name=":1">{{cite journal |vauthors=Bergen DJ, Kague E, Hammond CL |title=Zebrafish as an Emerging Model for Osteoporosis: A Primary Testing Platform for Screening New Osteo-Active Compounds |journal=Frontiers in Endocrinology |volume=10 |page=6 |date=2019 |pmid=30761080 |pmc=6361756 |doi=10.3389/fendo.2019.00006 |doi-access=free}}</ref> The (elasmoid) [[Fish scale#Elasmoid scales|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).<ref name=":1" /><ref>{{cite journal |vauthors=de Vrieze E, van Kessel MA, Peters HM, Spanings FA, Flik G, Metz JR |title=Prednisolone induces osteoporosis-like phenotype in regenerating zebrafish scales |journal=Osteoporosis International |volume=25 |issue=2 |pages=567–578 |date=February 2014 |pmid=23903952 |doi=10.1007/s00198-013-2441-3 |s2cid=21829206|hdl=2066/123472 |hdl-access=free}}</ref><ref>{{cite journal |vauthors=de Vrieze E, Zethof J, Schulte-Merker S, Flik G, Metz JR |title=Identification of novel osteogenic compounds by an ex-vivo sp7:luciferase zebrafish scale assay |journal=Bone |volume=74 |pages=106–113 |date=May 2015 |pmid=25600250 |doi=10.1016/j.bone.2015.01.006 |hdl=2066/153047 |hdl-access=free}}</ref>

=== 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.<ref name="Zang">{{cite journal |vauthors=Zang L, Maddison LA, Chen W |title=Zebrafish as a Model for Obesity and Diabetes |journal=Frontiers in Cell and Developmental Biology |volume=6 |issue=91 |page=91 |date=20 August 2018 |pmid=30177968 |pmc=6110173 |doi=10.3389/fcell.2018.00091 |doi-access=free}}</ref>

=== 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.<ref name="Zang" /> 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 melanocortin antagonist, showed increased body weight and adipose deposition during growth.<ref name="Zang" /> 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.<ref name="Zang" /> 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.<ref name="Zang" /> However, the normal fat, overfed specimens are still metabolically healthy, while high-fat diet specimens are not.<ref name="Zang" /> Understanding differences between types of feeding-induced obesity could prove useful in human treatment of obesity and related health conditions.<ref name="Zang" />

=== Environmental toxicology ===
Zebrafish have been used as a model system in [[environmental toxicology]] studies.<ref name="Hill 6–19"/>
=== Neurobiology ===
The combination of transparent zebrafish larva, [[light sheet fluorescence microscopy]], and [[calcium imaging|optical calcium indicators]] such as [[GCaMP]], allow the monitoring of all neurons in an awake, behaving animal.<ref>{{cite journal |title=Light-sheet functional imaging in fictively behaving Zebrafish |last1=Vladimirov |first1=Nikita |last2=Mu |first2=Yu |last3=Kawashima |first3=Takashi |last4=Bennett |first4=Davis V |last5=Yang |first5=Chao-Tsung |last6=Looger |first6=Loren L |last7=Keller |first7=Philipp J |last8=Freeman |first8=Jeremy |last9=Ahrens |first9=Misha B |author9-link=Misha B. Ahrens |journal=Nature Methods |volume=11 |number=9 |pages=883–884 |year=2014 |publisher=Nature Publishing Group US New York |doi= 10.1038/nmeth.3040 |pmid= 25068735 |url=https://www.nature.com/articles/nmeth.3040.pdf}}</ref>

=== 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.<ref>{{cite journal |vauthors=Cho SJ, Park E, Baker A, Reid AY |title=Age Bias in Zebrafish Models of Epilepsy: What Can We Learn From Old Fish? |journal=Frontiers in Cell and Developmental Biology |volume=8 |page=573303 |date=2020-09-10 |pmid=33015065 |pmc=7511771 |doi=10.3389/fcell.2020.573303 |doi-access=free}}</ref>