Hooked! Modeling human disease in zebrafish.

Zebrafish have been widely used as a model system for studying developmental processes, but in the last decade, they have also emerged as a valuable system for modeling human disease. The development and function of zebrafish organs are strikingly similar to those of humans, and the ease of creating mutant or transgenic fish has facilitated the generation of disease models. Here, we highlight the use of zebrafish for defining disease pathways and for discovering new therapies.

[1]  L. Kunkel,et al.  Drug screening in a zebrafish model of Duchenne muscular dystrophy , 2011, Proceedings of the National Academy of Sciences.

[2]  A. Emelyanov,et al.  Mifepristone-inducible LexPR system to drive and control gene expression in transgenic zebrafish. , 2008, Developmental biology.

[3]  M. Seabra,et al.  Translational bypass of nonsense mutations in zebrafish rep1, pax2.1 and lamb1 highlights a viable therapeutic option for untreatable genetic eye disease. , 2008, Human molecular genetics.

[4]  L. Ries,et al.  Cancer surveillance series: recent trends in childhood cancer incidence and mortality in the United States. , 1999, Journal of the National Cancer Institute.

[5]  M. Hendrix,et al.  The fate of human malignant melanoma cells transplanted into zebrafish embryos: Assessment of migration and cell division in the absence of tumor formation , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[6]  N. Schork,et al.  Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells. , 2007, Circulation.

[7]  M. Haldi,et al.  Human melanoma cells transplanted into zebrafish proliferate, migrate, produce melanin, form masses and stimulate angiogenesis in zebrafish , 2006, Angiogenesis.

[8]  Hiroshi Kikuta,et al.  Transgenesis in zebrafish with the tol2 transposon system. , 2009, Methods in molecular biology.

[9]  James F Amatruda,et al.  Zebrafish as a cancer model system. , 2002, Cancer cell.

[10]  L. Zon,et al.  Hematopoietic defects in rps29 mutant zebrafish depend upon p53 activation. , 2012, Experimental hematology.

[11]  L. Zon,et al.  T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. , 2010, Cancer cell.

[12]  Deborah A Nickerson,et al.  Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy. , 2011, American journal of human genetics.

[13]  L. Zon,et al.  Transparent adult zebrafish as a tool for in vivo transplantation analysis. , 2008, Cell stem cell.

[14]  Herwig Baier,et al.  Targeting neural circuitry in zebrafish using GAL4 enhancer trapping , 2007, Nature Methods.

[15]  A. Donovan,et al.  Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. , 2001, The Journal of clinical investigation.

[16]  L. Zon,et al.  tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Nancy Hopkins,et al.  Mutagenesis strategies in zebrafish for identifying genes involved in development and disease. , 2006, Trends in genetics : TIG.

[18]  B. Paw,et al.  montalcino, A zebrafish model for variegate porphyria. , 2008, Experimental hematology.

[19]  U. Langheinrich,et al.  Zebrafish: a new model on the pharmaceutical catwalk. , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[20]  Antonio J Giraldez,et al.  Evaluation and application of modularly assembled zinc-finger nucleases in zebrafish , 2011, Development.

[21]  Erin L. Doyle,et al.  Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting , 2011, Nucleic acids research.

[22]  A. Look,et al.  NOTCH1-induced T-cell leukemia in transgenic zebrafish , 2007, Leukemia.

[23]  T. Mizuno,et al.  Cell and tissue transplantation in zebrafish embryos. , 1999, Methods in molecular biology.

[24]  T. Südhof,et al.  Primary Role of Functional Ischemia, Quantitative Evidence for the Two-Hit Mechanism, and Phosphodiesterase-5 Inhibitor Therapy in Mouse Muscular Dystrophy , 2007, PloS one.

[25]  David M Langenau,et al.  Fluorescent imaging of cancer in zebrafish. , 2011, Methods in cell biology.

[26]  M. Noyes,et al.  Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases , 2008, Nature Biotechnology.

[27]  L. Zon,et al.  Chemical screening in zebrafish for novel biological and therapeutic discovery. , 2011, Methods in cell biology.

[28]  F. V. van Eeden,et al.  Zebrafish mutants in the von Hippel-Lindau tumor suppressor display a hypoxic response and recapitulate key aspects of Chuvash polycythemia. , 2009, Blood.

[29]  A. Brownlie,et al.  Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter , 2000, Nature.

[30]  J. Gross,et al.  Toward a better understanding of human eye disease insights from the zebrafish, Danio rerio. , 2011, Progress in molecular biology and translational science.

[31]  James M. Harris,et al.  Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models. , 2011, Cell stem cell.

[32]  Todd E. Scheetz,et al.  Somatic Mutagenesis with a Sleeping Beauty Transposon System Leads to Solid Tumor Formation in Zebrafish , 2011, PloS one.

[33]  David M Langenau,et al.  Myc-Induced T Cell Leukemia in Transgenic Zebrafish , 2003, Science.

[34]  M. Keating,et al.  Heart Regeneration in Zebrafish , 2002, Science.

[35]  Mark T. Handley,et al.  Loss-of-function mutations in RAB18 cause Warburg micro syndrome. , 2011, American journal of human genetics.

[36]  S. Revskoy,et al.  A new zebrafish model for experimental leukemia therapy , 2010, Cancer biology & therapy.

[37]  Bethan E. Hoskins,et al.  Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy. , 2010, The Journal of clinical investigation.

[38]  C. Macrae Cardiac arrhythmia: in vivo screening in the zebrafish to overcome complexity in drug discovery , 2010, Expert opinion on drug discovery.

[39]  Melinda Wenner The most transparent research , 2009, Nature Medicine.

[40]  S. L. Gonias,et al.  High-resolution imaging of the dynamic tumor cell–vascular interface in transparent zebrafish , 2007, Proceedings of the National Academy of Sciences.

[41]  Robert W. Mills,et al.  Novel Chemical Suppressors of Long QT Syndrome Identified by an In Vivo Functional Screen , 2011, Circulation.

[42]  N. Hukriede,et al.  Zebrafish kidney development: basic science to translational research. , 2011, Birth defects research. Part C, Embryo today : reviews.

[43]  Benjamin R. Lichman,et al.  Identification of adult nephron progenitors capable of kidney regeneration in zebrafish , 2011, Nature.

[44]  W. Dai,et al.  The conserved clusterin gene is expressed in the developing choroid plexus under the regulation of notch but not IGF signaling in zebrafish. , 2011, Endocrinology.

[45]  M. Lieber,et al.  The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. , 2010, Annual review of biochemistry.

[46]  John Postlethwait,et al.  Subfunction partitioning, the teleost radiation and the annotation of the human genome. , 2004, Trends in genetics : TIG.

[47]  D. Stemple TILLING — a high-throughput harvest for functional genomics , 2004, Nature Reviews Genetics.

[48]  Shuo Lin,et al.  Ribosomal protein S 19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p 53 protein family , 2008 .

[49]  Jiwoon Lee,et al.  Zebrafish blowout provides genetic evidence for Patched1-mediated negative regulation of Hedgehog signaling within the proximal optic vesicle of the vertebrate eye. , 2008, Developmental biology.

[50]  P. Currie,et al.  The zebrafish as a model for muscular dystrophy and congenital myopathy. , 2003, Human molecular genetics.

[51]  L. Zon,et al.  BRAF Mutations Are Sufficient to Promote Nevi Formation and Cooperate with p53 in the Genesis of Melanoma , 2005, Current Biology.

[52]  Christian Laggner,et al.  Rapid behavior—based identification of neuroactive small molecules in the zebrafish , 2009, Nature chemical biology.

[53]  Li Wang,et al.  Erratum: Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting (Nucleic Acids Research (2011) 39 (e82) DOI: 10.1093/nar/gkr218) , 2011 .

[54]  Rodney J Scott,et al.  P53 in human melanoma fails to regulate target genes associated with apoptosis and the cell cycle and may contribute to proliferation , 2011, BMC Cancer.

[55]  C. Brennan,et al.  Zebrafish behavioural assays of translational relevance for the study of psychiatric disease , 2011, Reviews in the neurosciences.

[56]  Martin Distel,et al.  Kita Driven Expression of Oncogenic HRAS Leads to Early Onset and Highly Penetrant Melanoma in Zebrafish , 2010, PloS one.

[57]  Charles Y. Lin,et al.  DHODH modulates transcriptional elongation in the neural crest and melanoma , 2011, Nature.

[58]  D A Kane,et al.  The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. , 1996, Development.

[59]  D. Ribatti,et al.  Mammalian tumor xenografts induce neovascularization in zebrafish embryos. , 2007, Cancer research.

[60]  M. Ekker,et al.  Modeling Neurodegeneration in Zebrafish , 2011, Current neurology and neuroscience reports.

[61]  J. Arluzea,et al.  Reprogramming of melanoma cells by embryonic microenvironments. , 2009, The International journal of developmental biology.

[62]  Shuo Lin,et al.  Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family. , 2008, Blood.

[63]  E. Rebar,et al.  Genome editing with engineered zinc finger nucleases , 2010, Nature Reviews Genetics.

[64]  D. Neuberg,et al.  Heat‐shock induction of T‐cell lymphoma/leukaemia in conditional Cre/lox‐regulated transgenic zebrafish , 2007, British journal of haematology.

[65]  Didier Y. R. Stainier,et al.  Cardiac troponin T is essential in sarcomere assembly and cardiac contractility , 2002, Nature Genetics.

[66]  L. Zon,et al.  Genetic Interaction of PGE2 and Wnt Signaling Regulates Developmental Specification of Stem Cells and Regeneration , 2009, Cell.

[67]  R. Plasterk,et al.  Target-selected gene inactivation in zebrafish. , 2004, Methods in cell biology.

[68]  N. Schork,et al.  Laminin-&agr;4 and Integrin-Linked Kinase Mutations Cause Human Cardiomyopathy Via Simultaneous Defects in Cardiomyocytes and Endothelial Cells , 2007 .

[69]  L. Zon,et al.  Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis , 2007, Nature.

[70]  H. Tamary,et al.  CURRENT DIAGNOSIS OF INHERITED BONE MARROW FAILURE SYNDROMES , 2007, Pediatric hematology and oncology.

[71]  Susan Carpenter,et al.  Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes , 2011, Nucleic acids research.

[72]  R. Roberts,et al.  A Dynamic Epicardial Injury Response Supports Progenitor Cell Activity during Zebrafish Heart Regeneration , 2006, Cell.

[73]  F. Baas,et al.  A frameshift mutation in LRSAM1 is responsible for a dominant hereditary polyneuropathy. , 2012, Human molecular genetics.

[74]  I. U. S. Leong,et al.  Disease modeling by gene targeting using microRNAs. , 2011, Methods in cell biology.

[75]  Akihiro Urasaki,et al.  zTrap: zebrafish gene trap and enhancer trap database , 2010, BMC Developmental Biology.

[76]  S. Haggarty,et al.  Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation , 2010, Science.

[77]  L. Zon,et al.  A New System for the Rapid Collection of Large Numbers of Developmentally Staged Zebrafish Embryos , 2011, PloS one.

[78]  Madeline A Lancaster,et al.  The primary cilium as a cellular signaling center: lessons from disease. , 2009, Current opinion in genetics & development.

[79]  A. Nicholson,et al.  Mutations of the BRAF gene in human cancer , 2002, Nature.

[80]  Qiling Xu,et al.  Microinjection and cell transplantation in zebrafish embryos. , 2008, Methods in molecular biology.

[81]  Ying Cao,et al.  Intraflagellar transport proteins are essential for cilia formation and for planar cell polarity. , 2010, Journal of the American Society of Nephrology : JASN.

[82]  M. Hendrix,et al.  Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma aggressiveness , 2006, Nature Medicine.

[83]  P. Beales,et al.  Restoration of renal function in zebrafish models of ciliopathies , 2008, Pediatric Nephrology.

[84]  Mark S. Miller,et al.  A genetic screen in zebrafish identifies cilia genes as a principal cause of cystic kidney , 2004, Development.

[85]  Lihua Julie Zhu,et al.  Zinc finger protein-dependent and -independent contributions to the in vivo off-target activity of zinc finger nucleases , 2010, Nucleic Acids Res..

[86]  L. Zon,et al.  Advanced zebrafish transgenesis with Tol2 and application for Cre/lox recombination experiments. , 2011, Methods in cell biology.

[87]  A. Schier,et al.  Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo. , 1996, Development.

[88]  P. Riley,et al.  Thymosin beta4 induces epicardium-derived neovascularization in the adult heart. , 2009, Biochemical Society transactions.

[89]  William A. Harris,et al.  Genetic Disorders of Vision Revealed by a Behavioral Screen of 400 Essential Loci in Zebrafish , 1999, The Journal of Neuroscience.

[90]  Mark C. Fishman,et al.  Cardiomyopathy in zebrafish due to mutation in an alternatively spliced exon of titin , 2002, Nature Genetics.

[91]  S. Leach,et al.  Zebrafish models for cancer. , 2011, Annual review of pathology.

[92]  Michael Lardelli,et al.  Zebrafish as a tool in Alzheimer's disease research. , 2011, Biochimica et biophysica acta.

[93]  Edwin Cuppen,et al.  Efficient target-selected mutagenesis in zebrafish. , 2003, Genome research.

[94]  E. Voest,et al.  LRRC50, a conserved ciliary protein implicated in polycystic kidney disease. , 2008, Journal of the American Society of Nephrology : JASN.

[95]  G. Rainer,et al.  The zebrafish heart regenerates after cryoinjury-induced myocardial infarction , 2011, BMC Developmental Biology.

[96]  Ann C. Morris,et al.  The genetics of ocular disorders: insights from the zebrafish. , 2011, Birth defects research. Part C, Embryo today : reviews.

[97]  L. Zon,et al.  Modeling Diamond Blackfan anemia in the zebrafish. , 2011, Seminars in hematology.

[98]  E. Olson,et al.  Transient Regenerative Potential of the Neonatal Mouse Heart , 2011, Science.

[99]  J. C. Belmonte,et al.  Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation , 2010, Nature.

[100]  K. Kawakami,et al.  Transient and stable transgenesis using tol2 transposon vectors. , 2009, Methods in molecular biology.

[101]  A. Chakraborty,et al.  Deficiency of ribosomal protein S19 during early embryogenesis leads to reduction of erythrocytes in a zebrafish model of Diamond-Blackfan anemia. , 2008, Human molecular genetics.

[102]  Dan M Roden,et al.  Drug-Sensitized Zebrafish Screen Identifies Multiple Genes, Including GINS3, as Regulators of Myocardial Repolarization , 2009, Circulation.

[103]  Christian Gieger,et al.  New gene functions in megakaryopoiesis and platelet formation , 2011, Nature.

[104]  J. Downing,et al.  Shared acquired genomic changes in zebrafish and human T-ALL , 2011, Oncogene.

[105]  C. Maki,et al.  Nutlin-3a Induces Cytoskeletal Rearrangement and Inhibits the Migration and Invasion Capacity of p53 Wild-Type Cancer Cells , 2010, Molecular Cancer Therapeutics.

[106]  Mark F. Lythgoe,et al.  De novo cardiomyocytes from within the activated adult heart after injury , 2011, Nature.

[107]  B. Paw,et al.  Characterization of zebrafish merlot/chablis as non-mammalian vertebrate models for severe congenital anemia due to protein 4.1 deficiency. , 2002, Development.

[108]  Leonard I Zon,et al.  Zebrafish tumor assays: the state of transplantation. , 2009, Zebrafish.

[109]  A. Brownlie,et al.  Positional cloning of the zebrafish sauternes gene: a model for congenital sideroblastic anaemia , 1998, Nature Genetics.