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The Power of Zebrafish in Personalised Medicine

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Personalised Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1007))

Abstract

The goal of personalised medicine is to develop tailor-made therapies for patients in whom currently available therapeutics fail. This approach requires correlating individual patient genotype data to specific disease phenotype data and using these stratified data sets to identify bespoke therapeutics. Applications for personalised medicine include common complex diseases which may have multiple targets, as well as rare monogenic disorders, for which the target may be unknown. In both cases, whole genome sequence analysis (WGS) is discovering large numbers of disease associated mutations in new candidate genes and potential modifier genes. Currently, the main limiting factor is the determination of which mutated genes are important for disease progression and therefore represent potential targets for drug discovery. Zebrafish have gained popularity as a model organism for understanding developmental processes, disease mechanisms and more recently for drug discovery and toxicity testing. In this chapter, we will examine the diverse roles that zebrafish can make in the expanding field of personalised medicine, from generating humanised disease models to xenograft screening of different cancer cell lines, through to finding new drugs via in vivo phenotypic screens. We will discuss the tools available for zebrafish research and recent advances in techniques, highlighting the advantages and potential of using zebrafish for high throughput disease modeling and precision drug discovery.

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References

  1. Davis EE, Frangakis S, Katsanis N (2014) Interpreting human genetic variation with in vivo zebrafish assays. Biochim Biophys Acta 1842:1960–1970. doi:10.1016/j.bbadis.2014.05.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Howe K et al (2013) The zebrafish reference genome sequence and its relationship to the human genome. Nature 496:498–503. doi:10.1038/nature12111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Cox DB, Platt RJ, Zhang F (2015) Therapeutic genome editing: prospects and challenges. Nat Med 21:121–131. doi:10.1038/nm.3793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Reardon S (2015) Leukaemia success heralds wave of gene-editing therapies. Nature 527:146–147. doi:10.1038/nature.2015.18737

    Article  CAS  PubMed  Google Scholar 

  5. Doyon Y et al (2008) Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 26:702–708. doi:10.1038/nbt1409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Meng X, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA (2008) Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat Biotechnol 26:695–701. doi:10.1038/nbt1398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sander JD et al (2011) Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat Methods 8:67–69. doi:10.1038/nmeth.1542

    Article  CAS  PubMed  Google Scholar 

  8. Cade L et al (2012) Highly efficient generation of heritable zebrafish gene mutations using homo- and heterodimeric TALENs. Nucleic Acids Res 40:8001–8010. doi:10.1093/nar/gks518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sander JD et al (2011) Targeted gene disruption in somatic zebrafish cells using engineered TALENs. Nat Biotechnol 29:697–698. doi:10.1038/nbt.1934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hwang WY et al (2013) Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol 31:227–229. doi:10.1038/nbt.2501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hruscha A et al (2013) Efficient CRISPR/Cas9 genome editing with low off-target effects in zebrafish. Development 140:4982–4987. doi:10.1242/dev.099085

    Article  CAS  PubMed  Google Scholar 

  12. Sertori R, Trengove M, Basheer F, Ward AC, Liongue C (2016) Genome editing in zebrafish: a practical overview. Brief Funct Genomics 15:322–330. doi:10.1093/bfgp/elv051

    Article  PubMed  Google Scholar 

  13. Ear J et al (2016) A zebrafish model of 5q-syndrome using CRISPR/Cas9 targeting RPS14 reveals a p53-independent and p53-dependent mechanism of erythroid failure. J Genet Genomics 43:307–318. doi:10.1016/j.jgg.2016.03.007

    Article  PubMed  Google Scholar 

  14. Zhang Y et al (2014) Defects of protein production in erythroid cells revealed in a zebrafish Diamond-Blackfan anemia model for mutation in RPS19. Cell Death Dis 5:e1352. doi:10.1038/cddis.2014.318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wilkinson RN, Jopling C, van Eeden FJ (2014) Zebrafish as a model of cardiac disease. Prog Mol Biol Transl Sci 124:65–91. doi:10.1016/B978-0-12-386930-2.00004-5

    Article  CAS  PubMed  Google Scholar 

  16. Wilkinson RN, van Eeden FJ (2014) The zebrafish as a model of vascular development and disease. Prog Mol Biol Transl Sci 124:93–122. doi:10.1016/B978-0-12-386930-2.00005-7

    Article  CAS  PubMed  Google Scholar 

  17. Schmid B, Haass C (2013) Genomic editing opens new avenues for zebrafish as a model for neurodegeneration. J Neurochem 127:461–470. doi:10.1111/jnc.12460

    Article  CAS  PubMed  Google Scholar 

  18. Martin-Jimenez R, Campanella M, Russell C (2015) New zebrafish models of neurodegeneration. Curr Neurol Neurosci Rep 15:33. doi:10.1007/s11910-015-0555-z

    Article  PubMed  CAS  Google Scholar 

  19. Auer TO, Duroure K, Concordet JP, Del Bene F (2014) CRISPR/Cas9-mediated conversion of eGFP- into Gal4-transgenic lines in zebrafish. Nat Protoc 9:2823–2840. doi:10.1038/nprot.2014.187

    Article  CAS  PubMed  Google Scholar 

  20. Auer TO, Duroure K, De Cian A, Concordet JP, Del Bene F (2014) Highly efficient CRISPR/Cas9-mediated knock-in in zebrafish by homology-independent DNA repair. Genome Res 24:142–153. doi:10.1101/gr.161638.113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shin J, Chen J, Solnica-Krezel L (2014) Efficient homologous recombination-mediated genome engineering in zebrafish using TALE nucleases. Development 141:3807–3818. doi:10.1242/dev.108019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zu Y et al (2013) TALEN-mediated precise genome modification by homologous recombination in zebrafish. Nat Methods 10:329–331. doi:10.1038/nmeth.2374

    Article  CAS  PubMed  Google Scholar 

  23. Armstrong GA et al (2016) Homology directed knockin of point mutations in the zebrafish tardbp and fus genes in ALS using the CRISPR/Cas9 system. PLoS One 11:–e0150188. doi:10.1371/journal.pone.0150188

  24. Bedell VM et al (2012) In vivo genome editing using a high-efficiency TALEN system. Nature 491:114–118. doi:10.1038/nature11537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gagnon JA et al (2014) Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs. PLoS One 9:e98186. doi:10.1371/journal.pone.0098186

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Hoshijima K, Jurynec MJ, Grunwald DJ (2016) Precise Editing of the Zebrafish Genome Made Simple and Efficient. Dev Cell 36:654–667. doi:10.1016/j.devcel.2016.02.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR (2016) Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533:420–424. doi:10.1038/nature17946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Amsterdam A et al (2004) Identification of 315 genes essential for early zebrafish development. Proc Natl Acad Sci U S A 101:12792–12797. doi:10.1073/pnas.0403929101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Driever W et al (1996) A genetic screen for mutations affecting embryogenesis in zebrafish. Development 123:37–46

    CAS  PubMed  Google Scholar 

  30. Haffter P et al (1996) The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development 123:1–36

    CAS  PubMed  Google Scholar 

  31. Kettleborough RN et al (2013) A systematic genome-wide analysis of zebrafish protein-coding gene function. Nature 496:494–497. doi:10.1038/nature11992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shah AN, Davey CF, Whitebirch AC, Miller AC, Moens CB (2015) Rapid reverse genetic screening using CRISPR in zebrafish. Nat Methods 12:535–540. doi:10.1038/nmeth.3360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kim IS et al (2017) Microenvironment-derived factors driving metastatic plasticity in melanoma. Nat Commun 8:14343. doi:10.1038/ncomms14343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sanjana NE (2016) Genome-scale CRISPR pooled screens. Anal Biochem. doi:10.1016/j.ab.2016.05.014

  35. Tsai SQ, Joung JK (2016) Defining and improving the genome-wide specificities of CRISPR-Cas9 nucleases. Nat Rev Genet 17:300–312. doi:10.1038/nrg.2016.28

    Article  CAS  PubMed  Google Scholar 

  36. Kleinstiver BP et al (2016) High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature 529:490–495. doi:10.1038/nature16526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Feng Y et al (2016) Expanding CRISPR/Cas9 genome editing capacity in zebrafish using SaCas9. G3 (Bethesda) 6:2517–2521. doi:10.1534/g3.116.031914

    Article  Google Scholar 

  38. Kleinstiver BP et al (2016) Genome-wide specificities of CRISPR-Cas Cpf1 nucleases in human cells. Nat Biotechnol 34:869–874. doi:10.1038/nbt.3620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kok FO et al (2015) Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish. Dev Cell 32:97–108. doi:10.1016/j.devcel.2014.11.018

    Article  CAS  PubMed  Google Scholar 

  40. Novodvorsky P et al (2015) klf2ash317 mutant zebrafish do not recapitulate morpholino-induced vascular and haematopoietic phenotypes. PLoS One 10:e0141611. doi:10.1371/journal.pone.0141611

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Shmukler BE et al (2015) Homozygous knockout of the piezo1 gene in the zebrafish is not associated with anemia. Haematologica 100:e483–e485. doi:10.3324/haematol.2015.132449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Rossi A et al (2015) Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature 524:230–233. doi:10.1038/nature14580

    Article  CAS  PubMed  Google Scholar 

  43. Diss G et al (2017) Gene duplication can impart fragility, not robustness, in the yeast protein interaction network. Science 355:630–634. doi:10.1126/science.aai7685

    Article  CAS  PubMed  Google Scholar 

  44. Runtuwene V et al (2011) Noonan syndrome gain-of-function mutations in NRAS cause zebrafish gastrulation defects. Dis Model Mech 4:393–399. doi:10.1242/dmm.007112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sousa SB et al (2014) Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome. Nat Genet 46:70–76. doi:10.1038/ng.2829

    Article  CAS  PubMed  Google Scholar 

  46. Thermes V et al (2002) I-SceI meganuclease mediates highly efficient transgenesis in fish. Mech Dev 118:91–98

    Article  CAS  PubMed  Google Scholar 

  47. Kawakami K et al (2004) A transposon-mediated gene trap approach identifies developmentally regulated genes in zebrafish. Dev Cell 7:133–144. doi:10.1016/j.devcel.2004.06.005

    Article  CAS  PubMed  Google Scholar 

  48. Mosimann C et al (2013) Site-directed zebrafish transgenesis into single landing sites with the phiC31 integrase system. Dev Dyn 242:949–963. doi:10.1002/dvdy.23989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Roberts JA et al (2014) Targeted transgene integration overcomes variability of position effects in zebrafish. Development 141:715–724. doi:10.1242/dev.100347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Langenau DM et al (2003) Myc-induced T cell leukemia in transgenic zebrafish. Science 299:887–890. doi:10.1126/science.1080280

    Article  CAS  PubMed  Google Scholar 

  51. Feng H et al (2007) Heat-shock induction of T-cell lymphoma/leukaemia in conditional Cre/lox-regulated transgenic zebrafish. Br J Haematol 138:169–175. doi:10.1111/j.1365-2141.2007.06625.x

    Article  CAS  PubMed  Google Scholar 

  52. Chen J et al (2007) NOTCH1-induced T-cell leukemia in transgenic zebrafish. Leukemia 21:462–471. doi:10.1038/sj.leu.2404546

    Article  PubMed  CAS  Google Scholar 

  53. Feng H et al (2010) T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. Cancer Cell 18:353–366. doi:10.1016/j.ccr.2010.09.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Patton EE et al (2005) BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma. Curr Biol 15:249–254. doi:10.1016/j.cub.2005.01.031

    Article  CAS  PubMed  Google Scholar 

  55. Davies H et al (2002) Mutations of the BRAF gene in human cancer. Nature 417:949–954. doi:10.1038/nature00766

    Article  CAS  PubMed  Google Scholar 

  56. O'Donnell KC et al (2014) Axon degeneration and PGC-1alpha-mediated protection in a zebrafish model of alpha-synuclein toxicity. Dis Model Mech 7:571–582. doi:10.1242/dmm.013185

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Ohki Y et al (2017) Glycine-alanine dipeptide repeat protein contributes to toxicity in a zebrafish model of C9orf72 associated neurodegeneration. Mol Neurodegener 12:6. doi:10.1186/s13024-016-0146-8

    Article  PubMed  PubMed Central  Google Scholar 

  58. Jindal GA et al (2017) In vivo severity ranking of Ras pathway mutations associated with developmental disorders. Proc Natl Acad Sci U S A 114:510–515. doi:10.1073/pnas.1615651114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Tsetskhladze ZR et al (2012) Functional assessment of human coding mutations affecting skin pigmentation using zebrafish. PLoS One 7:e47398. doi:10.1371/journal.pone.0047398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Waters MF et al (2006) Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat Genet 38:447–451. doi:10.1038/ng1758

    Article  CAS  PubMed  Google Scholar 

  61. Issa FA, Mazzochi C, Mock AF, Papazian DM (2011) Spinocerebellar ataxia type 13 mutant potassium channel alters neuronal excitability and causes locomotor deficits in zebrafish. J Neurosci 31:6831–6841. doi:10.1523/JNEUROSCI.6572-10.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Gonzaga-Jauregui C et al (2015) Exome sequence analysis suggests that genetic burden contributes to phenotypic variability and complex neuropathy. Cell Rep 12:1169–1183. doi:10.1016/j.celrep.2015.07.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Bedell VM, Westcot SE, Ekker SC (2011) Lessons from morpholino-based screening in zebrafish. Brief Funct Genomics 10:181–188. doi:10.1093/bfgp/elr021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Sia D, Moeini A, Labgaa I, Villanueva A (2015) The future of patient-derived tumor xenografts in cancer treatment. Pharmacogenomics 16:1671–1683. doi:10.2217/pgs.15.102

    Article  CAS  PubMed  Google Scholar 

  65. Malaney P, Nicosia SV, Dave V (2014) One mouse, one patient paradigm: new avatars of personalized cancer therapy. Cancer Lett 344:1–12. doi:10.1016/j.canlet.2013.10.010

    Article  CAS  PubMed  Google Scholar 

  66. Garralda E et al (2014) Integrated next-generation sequencing and avatar mouse models for personalized cancer treatment. Clin Cancer Res 20:2476–2484. doi:10.1158/1078-0432.CCR-13-3047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lam SH, Chua HL, Gong Z, Lam TJ, Sin YM (2004) Development and maturation of the immune system in zebrafish, Danio rerio: a gene expression profiling, in situ hybridization and immunological study. Dev Comp Immunol 28:9–28

    Article  CAS  PubMed  Google Scholar 

  68. Pelster B, Burggren WW (1996) Disruption of hemoglobin oxygen transport does not impact oxygen-dependent physiological processes in developing embryos of zebra fish (Danio rerio). Circ Res 79:358–362

    Article  CAS  PubMed  Google Scholar 

  69. Rouhi P et al (2010) Hypoxia-induced metastasis model in embryonic zebrafish. Nat Protoc 5:1911–1918. doi:10.1038/nprot.2010.150

    Article  CAS  PubMed  Google Scholar 

  70. Schnurr ME, Yin Y, Scott GR (2014) Temperature during embryonic development has persistent effects on metabolic enzymes in the muscle of zebrafish. J Exp Biol 217:1370–1380. doi:10.1242/jeb.094037

    Article  CAS  PubMed  Google Scholar 

  71. Haldi M, Ton C, Seng WL, McGrath P (2006) Human melanoma cells transplanted into zebrafish proliferate, migrate, produce melanin, form masses and stimulate angiogenesis in zebrafish. Angiogenesis 9:139–151. doi:10.1007/s10456-006-9040-2

    Article  PubMed  Google Scholar 

  72. Spence R, Gerlach G, Lawrence C, Smith C (2008) The behaviour and ecology of the zebrafish, Danio rerio. Biol Rev Camb Philos Soc 83:13–34. doi:10.1111/j.1469-185X.2007.00030.x

    Article  PubMed  Google Scholar 

  73. Tulotta C et al (2016) Imaging of human cancer cell proliferation, invasion, and micrometastasis in a zebrafish xenogeneic engraftment model. Methods Mol Biol 1451:155–169. doi:10.1007/978-1-4939-3771-4_11

    Article  PubMed  Google Scholar 

  74. Drabsch Y, He S, Zhang L, Snaar-Jagalska BE, ten Dijke P (2013) Transforming growth factor-beta signalling controls human breast cancer metastasis in a zebrafish xenograft model. Breast Cancer Res 15:R106. doi:10.1186/bcr3573

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Pruvot B et al (2011) Leukemic cell xenograft in zebrafish embryo for investigating drug efficacy. Haematologica 96:612–616. doi:10.3324/haematol.2010.031401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Nicoli S, Ribatti D, Cotelli F, Presta M (2007) Mammalian tumor xenografts induce neovascularization in zebrafish embryos. Cancer Res 67:2927–2931. doi:10.1158/0008-5472.CAN-06-4268

    Article  CAS  PubMed  Google Scholar 

  77. He S et al (2012) Neutrophil-mediated experimental metastasis is enhanced by VEGFR inhibition in a zebrafish xenograft model. J Pathol 227:431–445. doi:10.1002/path.4013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Jung DW et al (2012) A novel zebrafish human tumor xenograft model validated for anti-cancer drug screening. Mol BioSyst 8:1930–1939. doi:10.1039/c2mb05501e

    Article  CAS  PubMed  Google Scholar 

  79. White RM et al (2008) Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell 2:183–189. doi:10.1016/j.stem.2007.11.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Stoletov K, Montel V, Lester RD, Gonias SL, Klemke R (2007) High-resolution imaging of the dynamic tumor cell vascular interface in transparent zebrafish. Proc Natl Acad Sci U S A 104:17406–17411. doi:10.1073/pnas.0703446104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Tang Q et al (2014) Optimized cell transplantation using adult rag2 mutant zebrafish. Nat Methods 11:821–824. doi:10.1038/nmeth.3031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Jung IH et al (2016) Impaired lymphocytes development and xenotransplantation of gastrointestinal tumor cells in Prkdc-Null SCID zebrafish model. Neoplasia 18:468–479. doi:10.1016/j.neo.2016.06.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Zhang B et al (2016) Novel immunologic tolerance of human cancer cell xenotransplants in zebrafish. Transl Res 170:89–98 e81–83. doi:10.1016/j.trsl.2015.12.007

    Article  CAS  PubMed  Google Scholar 

  84. Bentley VL et al (2015) Focused chemical genomics using zebrafish xenotransplantation as a pre-clinical therapeutic platform for T-cell acute lymphoblastic leukemia. Haematologica 100:70–76. doi:10.3324/haematol.2014.110742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Rampazzo E et al (2013) Wnt activation promotes neuronal differentiation of glioblastoma. Cell Death Dis 4:e500. doi:10.1038/cddis.2013.32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Marques IJ et al (2009) Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model. BMC Cancer 9:128. doi:10.1186/1471-2407-9-128

    Article  PubMed  PubMed Central  Google Scholar 

  87. Mercatali, L. et al (2016) Development of a patient-derived xenograft (PDX) of breast cancer bone metastasis in a zebrafish model. Int J Mol Sci 17, doi:10.3390/ijms17081375

    Google Scholar 

  88. Gaudenzi G et al (2016) Patient-derived xenograft in zebrafish embryos: a new platform for translational research in neuroendocrine tumors. Endocrine. doi:10.1007/s12020-016-1048-9

  89. Lin J et al (2016) A clinically relevant in vivo zebrafish model of human multiple myeloma to study preclinical therapeutic efficacy. Blood 128:249–252. doi:10.1182/blood-2016-03-704460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Bansal N et al (2014) Enrichment of human prostate cancer cells with tumor initiating properties in mouse and zebrafish xenografts by differential adhesion. Prostate 74:187–200. doi:10.1002/pros.22740

    Article  CAS  PubMed  Google Scholar 

  91. Staal FJ, Spaink HP, Fibbe WE (2016) Visualizing human hematopoietic stem cell trafficking in vivo using a zebrafish xenograft model. Stem Cells Dev 25:360–365. doi:10.1089/scd.2015.0195

    Article  CAS  PubMed  Google Scholar 

  92. Li J et al (2015) Xenotransplantation of human adipose-derived stem cells in zebrafish embryos. PLoS One 10:e0123264. doi:10.1371/journal.pone.0123264

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Patel N et al (2012) Developmental regulation of TAC1 in peptidergic-induced human mesenchymal stem cells: implication for spinal cord injury in zebrafish. Stem Cells Dev 21:308–320. doi:10.1089/scd.2011.0179

    Article  CAS  PubMed  Google Scholar 

  94. Xia H et al (2014) Identification of a cell-of-origin for fibroblasts comprising the fibrotic reticulum in idiopathic pulmonary fibrosis. Am J Pathol 184:1369–1383. doi:10.1016/j.ajpath.2014.01.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Lee LM, Seftor EA, Bonde G, Cornell RA, Hendrix MJ (2005) The fate of human malignant melanoma cells transplanted into zebrafish embryos: assessment of migration and cell division in the absence of tumor formation. Dev Dyn 233:1560–1570. doi:10.1002/dvdy.20471

    Article  CAS  PubMed  Google Scholar 

  96. Benyumov AO et al (2012) A novel zebrafish embryo xenotransplantation model to study primary human fibroblast motility in health and disease. Zebrafish 9:38–43. doi:10.1089/zeb.2011.0705

    Article  PubMed  PubMed Central  Google Scholar 

  97. Chan XY et al (2015) Three- dimensional vascular network assembly from diabetic patient-derived induced pluripotent stem cells. Arterioscler Thromb Vasc Biol 35:2677–2685. doi:10.1161/ATVBAHA.115.306362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Orlova VV et al (2014) Functionality of endothelial cells and pericytes from human pluripotent stem cells demonstrated in cultured vascular plexus and zebrafish xenografts. Arterioscler Thromb Vasc Biol 34:177–186. doi:10.1161/ATVBAHA.113.302598

    Article  CAS  PubMed  Google Scholar 

  99. Orlova VV et al (2014) Generation, expansion and functional analysis of endothelial cells and pericytes derived from human pluripotent stem cells. Nat Protoc 9:1514–1531. doi:10.1038/nprot.2014.102

    Article  CAS  PubMed  Google Scholar 

  100. MacRae CA, Peterson RT (2015) Zebrafish as tools for drug discovery. Nat Rev Drug Discov 14:721–731. doi:10.1038/nrd4627

    Article  CAS  PubMed  Google Scholar 

  101. Strange K (2016) Drug discovery in fish, flies, and worms. ILAR J 57:133–143. doi:10.1093/ilar/ilw034

    Article  PubMed  Google Scholar 

  102. Swinney DC (2013) Phenotypic vs. target-based drug discovery for first-in-class medicines. Clin Pharmacol Ther 93:299–301. doi:10.1038/clpt.2012.236

    Article  CAS  PubMed  Google Scholar 

  103. Peterson RT, Link BA, Dowling JE, Schreiber SL (2000) Small molecule developmental screens reveal the logic and timing of vertebrate development. Proc Natl Acad Sci U S A 97:12965–12969. doi:10.1073/pnas.97.24.12965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Rennekamp AJ, Peterson RT (2015) 15 years of zebrafish chemical screening. Curr Opin Chem Biol 24:58–70. doi:10.1016/j.cbpa.2014.10.025

    Article  CAS  PubMed  Google Scholar 

  105. Baxendale S et al (2012) Identification of compounds with anti-convulsant properties in a zebrafish model of epileptic seizures. Dis Model Mech 5:773–784. doi:10.1242/dmm.010090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. North TE et al (2007) Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 447:1007–1011. doi:10.1038/nature05883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Robertson AL et al (2014) A zebrafish compound screen reveals modulation of neutrophil reverse migration as an anti-inflammatory mechanism. Sci Transl Med 6:225ra229. doi:10.1126/scitranslmed.3007672

    Article  CAS  Google Scholar 

  108. Gallardo VE et al (2015) Phenotype-driven chemical screening in zebrafish for compounds that inhibit collective cell migration identifies multiple pathways potentially involved in metastatic invasion. Dis Model Mech 8:565–576. doi:10.1242/dmm.018689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Kokel D et al (2010) Rapid behavior-based identification of neuroactive small molecules in the zebrafish. Nat Chem Biol 6:231–237. doi:10.1038/nchembio.307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Rihel J et al (2010) Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation. Science 327:348–351. doi:10.1126/science.1183090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Asimaki A et al (2014) Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy. Sci Transl Med 6:240ra274. doi:10.1126/scitranslmed.3008008

    Article  CAS  Google Scholar 

  112. Peal DS et al (2011) Novel chemical suppressors of long QT syndrome identified by an in vivo functional screen. Circulation 123:23–30. doi:10.1161/CIRCULATIONAHA.110.003731

    Article  PubMed  Google Scholar 

  113. Yeh JR et al (2008) AML1-ETO reprograms hematopoietic cell fate by downregulating scl expression. Development 135:401–410. doi:10.1242/dev.008904

    Article  CAS  PubMed  Google Scholar 

  114. Owens KN et al (2008) Identification of genetic and chemical modulators of zebrafish mechanosensory hair cell death. PLoS Genet 4:e1000020. doi:10.1371/journal.pgen.1000020

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. White RM et al (2011) DHODH modulates transcriptional elongation in the neural crest and melanoma. Nature 471:518–522. doi:10.1038/nature09882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Kaufman CK et al (2016) A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation. Science 351:aad2197. doi:10.1126/science.aad2197

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Kalueff AV et al (2013) Towards a comprehensive catalog of zebrafish behavior 1.0 and beyond. Zebrafish 10:70–86. doi:10.1089/zeb.2012.0861

    Article  PubMed  PubMed Central  Google Scholar 

  118. Kalueff AV et al (2016) Zebrafish neurobehavioral phenomics for aquatic neuropharmacology and toxicology research. Aquat Toxicol 170:297–309. doi:10.1016/j.aquatox.2015.08.007

    Article  CAS  PubMed  Google Scholar 

  119. Stewart AM et al (2015) A novel 3D method of locomotor analysis in adult zebrafish: implications for automated detection of CNS drug-evoked phenotypes. J Neurosci Methods 255:66–74. doi:10.1016/j.jneumeth.2015.07.023

    Article  PubMed  Google Scholar 

  120. Rennekamp AJ et al (2016) sigma1 receptor ligands control a switch between passive and active threat responses. Nat Chem Biol 12:552–558. doi:10.1038/nchembio.2089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Bruni G et al (2016) Zebrafish behavioral profiling identifies multitarget antipsychotic-like compounds. Nat Chem Biol 12:559–566. doi:10.1038/nchembio.2097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Cunliffe VT (2016) Building a zebrafish toolkit for investigating the pathobiology of epilepsy and identifying new treatments for epileptic seizures. J Neurosci Methods 260:91–95. doi:10.1016/j.jneumeth.2015.07.015

    Article  PubMed  Google Scholar 

  123. Winter MJ et al (2008) Validation of a larval zebrafish locomotor assay for assessing the seizure liability of early-stage development drugs. J Pharmacol Toxicol Methods 57:176–187. doi:10.1016/j.vascn.2008.01.004

    Article  CAS  PubMed  Google Scholar 

  124. Baraban SC, Taylor MR, Castro PA, Baier H (2005) Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression. Neuroscience 131:759–768. doi:10.1016/j.neuroscience.2004.11.031

    Article  CAS  PubMed  Google Scholar 

  125. Dravet C, Bureau M, Oguni H, Fukuyama Y, Cokar O (2005) Severe myoclonic epilepsy in infancy: Dravet syndrome. Adv Neurol 95:71–102

    PubMed  Google Scholar 

  126. Baraban SC, Dinday MT, Hortopan GA (2013) Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet syndrome treatment. Nat Commun 4:2410. doi:10.1038/ncomms3410

    Article  PubMed  PubMed Central  Google Scholar 

  127. Griffin A et al (2017) Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome. Brain. doi:10.1093/brain/aww342

  128. Bracken MB (2009) Why animal studies are often poor predictors of human reactions to exposure. J R Soc Med 102:120–122. doi:10.1258/jrsm.2008.08k033

    Article  PubMed  PubMed Central  Google Scholar 

  129. Seok J et al (2013) Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A 110:3507–3512. doi:10.1073/pnas.1222878110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Rice J (2012) Animal models: not close enough. Nature 484:S9

    Article  PubMed  Google Scholar 

  131. Eliceiri BP, Gonzalez AM, Baird A (2011) Zebrafish model of the blood-brain barrier: morphological and permeability studies. Methods Mol Biol 686:371–378. doi:10.1007/978-1-60761-938-3_18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Fleming A, Diekmann H, Goldsmith P (2013) Functional characterisation of the maturation of the blood-brain barrier in larval zebrafish. PLoS One 8:e77548. doi:10.1371/journal.pone.0077548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Tam SJ et al (2012) Death receptors DR6 and TROY regulate brain vascular development. Dev Cell 22:403–417. doi:10.1016/j.devcel.2011.11.018

    Article  CAS  PubMed  Google Scholar 

  134. Goldstone JV et al (2010) Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish. BMC Genomics 11:643. doi:10.1186/1471-2164-11-643

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  135. Verbueken E et al (2017) In vitro biotransformation of two human CYP3A probe substrates and their inhibition during early zebrafish development. Int J Mol Sci 18. doi:10.3390/ijms18010217

  136. Martignoni M, Groothuis G, de Kanter R (2006) Comparison of mouse and rat cytochrome P450-mediated metabolism in liver and intestine. Drug Metab Dispos 34:1047–1054. doi:10.1124/dmd.105.009035

    CAS  PubMed  Google Scholar 

  137. Poon KL et al (2016) Humanizing the zebrafish liver shifts drug metabolic profiles and improves pharmacokinetics of CYP3A4 substrates. Arch Toxicol. doi:10.1007/s00204-016-1789-5

  138. Gootenberg DB, Turnbaugh PJ (2011) Companion animals symposium: humanized animal models of the microbiome. J Anim Sci 89:1531–1537. doi:10.2527/jas.2010-3371

    Article  CAS  PubMed  Google Scholar 

  139. Rawls JF, Mahowald MA, Goodman AL, Trent CM, Gordon JI (2007) In vivo imaging and genetic analysis link bacterial motility and symbiosis in the zebrafish gut. Proc Natl Acad Sci U S A 104:7622–7627. doi:10.1073/pnas.0702386104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Wittbrodt JN, Liebel U, Gehrig J (2014) Generation of orientation tools for automated zebrafish screening assays using desktop 3D printing. BMC Biotechnol 14:36. doi:10.1186/1472-6750-14-36

    Article  PubMed  PubMed Central  Google Scholar 

  141. Yanik MF, Rohde CB, Pardo-Martin C (2011) Technologies for micromanipulating, imaging, and phenotyping small invertebrates and vertebrates. Annu Rev Biomed Eng 13:185–217. doi:10.1146/annurev-bioeng-071910-124703

    Article  CAS  PubMed  Google Scholar 

  142. Pulak R (2016) Tools for automating the imaging of zebrafish larvae. Methods 96:118–126. doi:10.1016/j.ymeth.2015.11.021

    Article  CAS  PubMed  Google Scholar 

  143. White DT et al (2016) ARQiv-HTS, a versatile whole-organism screening platform enabling in vivo drug discovery at high-throughput rates. Nat Protoc 11:2432–2453. doi:10.1038/nprot.2016.142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Collins FS, Varmus H (2015) A new initiative on precision medicine. N Engl J Med 372:793–795. doi:10.1056/NEJMp1500523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Gahl WA et al (2016) The NIH undiagnosed diseases program and network: applications to modern medicine. Mol Genet Metab 117:393–400. doi:10.1016/j.ymgme.2016.01.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Wienholds E, Schulte-Merker S, Walderich B, Plasterk RH (2002) Target-selected inactivation of the zebrafish rag1 gene. Science 297:99–102. doi:10.1126/science.1071762

    Article  CAS  PubMed  Google Scholar 

  147. Varshney GK et al (2013) The Zebrafish Insertion Collection (ZInC): a web based, searchable collection of zebrafish mutations generated by DNA insertion. Nucleic Acids Res 41:D861–D864. doi:10.1093/nar/gks946

    Article  CAS  PubMed  Google Scholar 

  148. Nasevicius A, Ekker SC (2000) Effective targeted gene ‘knockdown’ in zebrafish. Nat Genet 26:216–220. doi:10.1038/79951

    Article  CAS  PubMed  Google Scholar 

  149. Schulte-Merker S, Stainier DY (2014) Out with the old, in with the new: reassessing morpholino knockdowns in light of genome editing technology. Development 141:3103–3104. doi:10.1242/dev.112003

    Article  CAS  PubMed  Google Scholar 

  150. Larson MH et al (2013) CRISPR interference (CRISPRi) for sequence-specific control of gene expression. Nat Protoc 8:2180–2196. doi:10.1038/nprot.2013.132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Liu SJ et al (2017) CRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells. Science 355. doi:10.1126/science.aah7111

  152. Weber T, Koster R (2013) Genetic tools for multicolor imaging in zebrafish larvae. Methods 62:279–291. doi:10.1016/j.ymeth.2013.07.028

    Article  CAS  PubMed  Google Scholar 

  153. Halpern ME et al (2008) Gal4/UAS transgenic tools and their application to zebrafish. Zebrafish 5:97–110. doi:10.1089/zeb.2008.0530

    Article  CAS  PubMed  Google Scholar 

  154. Mosimann C, Zon LI (2011) Advanced zebrafish transgenesis with Tol2 and application for Cre/lox recombination experiments. Methods Cell Biol 104:173–194. doi:10.1016/B978-0-12-374814-0.00010-0

    Article  PubMed  CAS  Google Scholar 

  155. Pan YA et al (2013) Zebrabow: multispectral cell labeling for cell tracing and lineage analysis in zebrafish. Development 140:2835–2846. doi:10.1242/dev.094631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Henninger J et al (2017) Clonal fate mapping quantifies the number of haematopoietic stem cells that arise during development. Nat Cell Biol 19:17–27. doi:10.1038/ncb3444

    Article  CAS  PubMed  Google Scholar 

  157. Moro E et al (2013) Generation and application of signaling pathway reporter lines in zebrafish. Mol Gen Genomics 288:231–242. doi:10.1007/s00438-013-0750-z

    Article  CAS  Google Scholar 

  158. Shimozono S, Iimura T, Kitaguchi T, Higashijima S, Miyawaki A (2013) Visualization of an endogenous retinoic acid gradient across embryonic development. Nature 496:363–366. doi:10.1038/nature12037

    Article  CAS  PubMed  Google Scholar 

  159. Thisse B, Thisse C (2014) In situ hybridization on whole-mount zebrafish embryos and young larvae. Methods Mol Biol 1211:53–67. doi:10.1007/978-1-4939-1459-3_5

    Article  CAS  PubMed  Google Scholar 

  160. Choi HM et al (2016) Mapping a multiplexed zoo of mRNA expression. Development 143:3632–3637. doi:10.1242/dev.140137

    Article  CAS  PubMed  Google Scholar 

  161. Dang M, Henderson RE, Garraway LA, Zon LI (2016) Long-term drug administration in the adult zebrafish using oral gavage for cancer preclinical studies. Dis Model Mech 9:811–820. doi:10.1242/dmm.024166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Olt J, Allen CE, Marcotti W (2016) In vivo physiological recording from the lateral line of juvenile zebrafish. J Physiol 594:5427–5438. doi:10.1113/JP271794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Keller PJ (2013) In vivo imaging of zebrafish embryogenesis. Methods 62:268–278. doi:10.1016/j.ymeth.2013.03.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Burgess HA, Granato M (2007) Sensorimotor gating in larval zebrafish. J Neurosci 27:4984–4994. doi:10.1523/JNEUROSCI.0615-07.2007

    Article  CAS  PubMed  Google Scholar 

  165. Weber M, Huisken J (2015) In vivo imaging of cardiac development and function in zebrafish using light sheet microscopy. Swiss Med Wkly 145:w14227. doi:10.4414/smw.2015.14227

    PubMed  Google Scholar 

  166. Muto A, Kawakami K (2011) Imaging functional neural circuits in zebrafish with a new GCaMP and the Gal4FF-UAS system. Commun Integr Biol 4:566–568. doi:10.4161/cib.4.5.15848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Prajsnar TK, Cunliffe VT, Foster SJ, Renshaw SA (2008) A novel vertebrate model of Staphylococcus aureus infection reveals phagocyte-dependent resistance of zebrafish to non-host specialized pathogens. Cell Microbiol 10:2312–2325. doi:10.1111/j.1462-5822.2008.01213.x

    Article  CAS  PubMed  Google Scholar 

  168. Bojarczuk A et al (2016) Cryptococcus neoformans intracellular proliferation and capsule size determines early macrophage control of infection. Sci Report 6:21489. doi:10.1038/srep21489

    Article  CAS  Google Scholar 

  169. Harvey SA et al (2013) Identification of the zebrafish maternal and paternal transcriptomes. Development 140:2703–2710. doi:10.1242/dev.095091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Wardle FC, Muller F (2014) Fish genomics: casting the net wide. Brief Funct Genomics 13:79–81. doi:10.1093/bfgp/elt055

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank Vincent Cunliffe for comments on the manuscript. SB is funded by a grant from the BBSRC (BB/M01021X/1) and FvE was funded by BBSRC (BB/M02332X/1). The Sheffield zebrafish aquarium and small molecule screening facilities are supported by grants from the MRC (G0700091, G0802527).

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  1. The Bateson Centre, Department of Biomedical Science, University of Sheffield, Sheffield, S10 2TN, UK

    Sarah Baxendale, Freek van Eeden & Robert Wilkinson

  2. Department of Infection, Immunity and Cardiovascular Disease, Medical School, Beech Hill Rd, University of Sheffield, Sheffield, S10 2RX, UK

    Robert Wilkinson

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  1. Sarah Baxendale
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  2. Freek van Eeden
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  3. Robert Wilkinson
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Correspondence to Sarah Baxendale .

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  1. Krebs Institute and Sheffield Institute for Nucleic Acids, Department of Molecular Biology and Biotechnology, Firth Court, University of Sheffield, Sheffield, United Kingdom

    Sherif El-Khamisy

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Baxendale, S., van Eeden, F., Wilkinson, R. (2017). The Power of Zebrafish in Personalised Medicine. In: El-Khamisy, S. (eds) Personalised Medicine. Advances in Experimental Medicine and Biology, vol 1007. Springer, Cham. https://doi.org/10.1007/978-3-319-60733-7_10

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