Zebrafish and Medaka: new model organisms for modern biomedical research

Journal of Biomedical Science - Tập 23 - Trang 1-11 - 2016
Cheng-Yung Lin1, Cheng-Yi Chiang1, Huai-Jen Tsai1
1Graduate Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan

Tóm tắt

Although they are primitive vertebrates, zebrafish (Danio rerio) and medaka (Oryzias latipes) have surpassed other animals as the most used model organisms based on their many advantages. Studies on gene expression patterns, regulatory cis-elements identification, and gene functions can be facilitated by using zebrafish embryos via a number of techniques, including transgenesis, in vivo transient assay, overexpression by injection of mRNAs, knockdown by injection of morpholino oligonucleotides, knockout and gene editing by CRISPR/Cas9 system and mutagenesis. In addition, transgenic lines of model fish harboring a tissue-specific reporter have become a powerful tool for the study of biological sciences, since it is possible to visualize the dynamic expression of a specific gene in the transparent embryos. In particular, some transgenic fish lines and mutants display defective phenotypes similar to those of human diseases. Therefore, a wide variety of fish model not only sheds light on the molecular mechanisms underlying disease pathogenesis in vivo but also provides a living platform for high-throughput screening of drug candidates. Interestingly, transgenic model fish lines can also be applied as biosensors to detect environmental pollutants, and even as pet fish to display beautiful fluorescent colors. Therefore, transgenic model fish possess a broad spectrum of applications in modern biomedical research, as exampled in the following review.

Tài liệu tham khảo

Hackett PB. The molecular biology of transgenic fish. In: Hochachka PW, Mommsen TP, editors. Biochemistry and Molecular Biology of Fishes. Amsterdam: Elsevier Science; 1993. p. 207–40. Hsiao CD, Hsieh FJ, Tsai HJ. Enhanced expression and stable transmission of transgenes flanked by inverted terminal repeats from adeno-associated virus in zebrafish. Dev Dyn. 2001;220:323–36. Kawakami K, Shima A. Identification of the Tol2 transposase of the medaka fish Oryzias latipes that catalyzes excision of a nonautonomous Tol2 element in zebrafish Danio rerio. Gene. 1999;240:239–44. Urasaki A, Morvan G, Kawakami K. Functional dissection of the Tol2 transposable element identified the minimal cis-sequence and a highly repetitive sequence in the subterminal region essential for transposition. Genetics. 2006;174:639–49. Kawakami K, Takeda H, Kawakami N, Kobayashi M, Matsuda N, Mishina M. A transposon-mediated gene trap approach identifies developmentally regulated genes in zebrafish. Dev Cell. 2004;7:133–44. Huang P, Xiao A, Zhou M, Zhu Z, Lin S, Zhang B. Heritable gene targeting in zebrafish using customized TALENs. Nat Biotechnol. 2011;29:699–700. Hwang WY, Fu Y, Reyon D, Maeder ML, Tsai SQ, Sander JD, et al. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol. 2013;31:227–9. Auer TO, Del Bene F. CRISPR/Cas9 and TALEN-mediated knock-in approaches in zebrafish. Methods. 2014;69:142–50. Amsterdam A, Lin S, Hopkins N. The Aequorea victoria green fluorescent protein can be used as a reporter in live zebrafish embryos. Dev Biol. 1995;171:123–9. Long Q, Meng A, Wang H, Jessen JR, Farrell MJ, Lin S. GATA-1 expression pattern can be recapitulated in living transgenic zebrafish using GFP reporter gene. Development. 1997;124:4105–11. Higashijima S, Okamoto H, Ueno N, Hotta Y, Eguchi G. High-frequency generation of transgenic zebrafish which reliably express GFP in whole muscles or the whole body by using promoters of zebrafish origin. Dev Biol. 1997;192:289–99. Kennedy BN, Vihtelic TS, Checkley L, Vaughan KT, Hyde DR. Isolation of a zebrafish rod opsin promoter to generate a transgenic zebrafish line expressing enhanced green fluorescent protein in rod photoreceptors. J Biol Chem. 2001;276:14037–43. Higashijima S, Hotta Y, Okamoto H. Visualization of cranial motor neurons in live transgenic zebrafish expressing green fluorescent protein under the control of the islet-1 promoter/enhancer. J Neurosci. 2000;20:206–18. Huang H, Vogel SS, Liu N, Melton DA, Lin S. Analysis of pancreatic development in living transgenic zebrafish embryos. Mol Cell Endocrinol. 2001;177:117–24. Huang CJ, Tu CT, Hsiao CD, Hsieh FJ, Tsai HJ. Germ-line transmission of a myocardium-specific GFP transgene reveals critical regulatory elements in the cardiac myosin light chain 2 promoter of zebrafish. Dev Dyn. 2003;228:30–40. Her GM, Yeh YH, Wu JL. 435-bp liver regulatory sequence in the liver fatty acid binding protein (L-FABP) gene is sufficient to modulate liver regional expression in transgenic zebrafish. Dev Dyn. 2003;227:347–56. Kim YI, Lee S, Jung SH, Kim HT, Choi JH, Lee MS, et al. Establishment of a bone-specific col10a1: GFP transgenic zebrafish. Mol Cells. 2013;36:145–50. Walton EM, Cronan MR, Beerman RW, Tobin DM. The macrophage-specific promoter mfap4 allows live, long-term analysis of macrophage behavior during mycobacterial infection in zebrafish. PLoS One. 2015;10, e0138949. Krøvel AV, Olsen LC. Expression of a vas:: EGFP transgene in primordial germ cells of the zebrafish. Mech Dev. 2002;116:141–50. Chou CY, Horng LS, Tsai HJ. Uniform GFP-expression in transgenic medaka (Oryzias latipes) at the F0 generation. Transgenic Res. 2001;10:303–15. Holden C, Bhattacharjee Y. Random samples: That special glow. Science. 2003;300:1368. Dean J. Genetics: Fish that glow in Taiwan. Far Eastern Economic Review. 2003;8:38. Buechner MM, Grossman L, Hamilton A. Coolest inventions 2003: Light and dark-Red fish, blue fish and Glow-in-dark fish. TIME. 2003;24:68–9. Jessen JR, Meng A, McFarlane RJ, Paw BH, Zon LI, Smith GR, et al. Modification of bacterial artificial chromosomes through chi-stimulated homologous recombination and its application in zebrafish transgenesis. Proc Natl Acad Sci U S A. 1998;95:5121–6. Jessen JR, Willett CE, Lin S. Artificial chromosome transgenesis reveals long-distance negative regulation of rag1 in zebrafish. Nat Genet. 1999;23:15–6. Chen YH, Wang YH, Chang MY, Lin CY, Weng CW, Westerfield M, et al. Multiple upstream modules regulate zebrafish myf5 expression. BMC Dev Biol. 2007;7:1. Scheer N, Campos-Ortega JA. Use of the GAL4-UAS technique for targeted gene expression in zebrafish. Mech Dev. 1999;80:153–8. Walsh EC, Stainier DY. UDP-glucose dehydrogenase required for cardiac valve formation in zebrafish. Science. 2001;293:1670–3. Raya A, Koth CM, Büscher D, Kawakami Y, Itoh T, Raya RM, et al. Activation of Notch signaling pathway precedes heart regeneration in zebrafish. Proc Natl Acad Sci U S A. 2003;100 Suppl 1:11889–95. Shu X, Cheng K, Patel N, Chen F, Joseph E, Tsai HJ, et al. Na, K-ATPase is essential for embryonic heart development in the zebrafish. Development. 2003;130:6165–73. Forouhar AS, Liebling M, Hickerson A, Nasiraei-Moghaddam A, Tsai HJ, Hove JR, et al. The embryonic vertebrate heart tube is a dynamic suction pump. Science. 2006;312:751–3. Liebling M, Forouhar AS, Gharib M, Fraser SE, Dickinson ME. Four-dimensional cardiac imaging in living embryos via postacquisition synchronization of nongated slice sequences. J Biomed Opt. 2005;10:054001. Hami D, Grimes AC, Tsai HJ, Kirby ML. Zebrafish cardiac development requires a conserved secondary heart field. Development. 2011;138:2389–98. Nevis K, Obregon P, Walsh C, Guner-Ataman B, Burns CG, Burns CE. Tbx1 is required for second heart field proliferation in zebrafish. Dev Dyn. 2013;242:550–9. Chen YH, Lee HC, Liu CF, Lin CY, Tsai HJ. Novel regulatory sequence − 82/-62 functions as a key element to drive the somite-specificity of zebrafish myf-5. Dev Dyn. 2003;228:41–50. Lee HC, Huang HY, Lin CY, Chen YH, Tsai HJ. Foxd3 mediates zebrafish myf5 expression during early somitogenesis. Dev Biol. 2006;290:359–72. Lee HC, Tseng WA, Lo FY, Liu TM, Tsai HJ. FoxD5 mediates anterior-posterior polarity through upstream modulator Fgf signaling during zebrafish somitogenesis. Dev Biol. 2009;336:232–45. Wang YH, Li CK, Lee GH, Tsay HJ, Tsai HJ, Chen YH. Inactivation of zebrafish mrf4 leads to myofibril misalignment and motor axon growth disorganization. Dev Dyn. 2008;237:1043–50. Lin CY, Chen YH, Lee HC, Tsai HJ. Novel cis-element in intron 1 represses somite expression of zebrafish myf-5. Gene. 2004;334:63–72. Lin CY, Chen JS, Loo MR, Hsiao CC, Chang WY, Tsai HJ. MicroRNA-3906 regulates fast muscle differentiation through modulating the target gene homer-1b in zebrafish embryos. PLoS One. 2013;8:e70187. Hsu RJ, Lin CY, Hoi HS, Zheng SK, Lin CC, Tsai HJ. Novel intronic microRNA represses zebrafish myf5 promoter activity through silencing dickkopf-3 gene. Nucleic Acids Res. 2010;38:4384–93. Fu CY, Su YF, Lee MH, Chang GD, Tsai HJ. Zebrafish Dkk3a protein regulates the activity of myf5 promoter through interaction with membrane receptor integrin α6b. J Biol Chem. 2012;287:40031–42. Hsu RJ, Lin CC, Su YF, Tsai HJ. dickkopf-3-related gene regulates the expression of zebrafish myf5 gene through phosphorylated p38a-dependent Smad4 activity. J Biol Chem. 2011;286:6855–64. Lin CY, Yung RF, Lee HC, Chen WT, Chen YH, Tsai HJ. Myogenic regulatory factors Myf5 and Myod function distinctly during craniofacial myogenesis of zebrafish. Dev Biol. 2006;299:594–608. Lin CY, Chen WT, Lee HC, Yang PH, Yang HJ, Tsai HJ. The transcription factor Six1a plays an essential role in the craniofacial myogenesis of zebrafish. Dev Biol. 2009;331:152–66. Lin CY, Lee HC, Chen HC, Hsieh CC, Tsai HJ. Normal function of Myf5 during gastrulation is required for pharyngeal arch cartilage development in zebrafish embryos. Zebrafish. 2013;10:486–99. Hinits Y, Osborn DP, Hughes SM. Differential requirements for myogenic regulatory factors distinguish medial and lateral somitic, cranial and fin muscle fibre populations. Development. 2009;136:403–14. Ma GC, Wang TM, Su CY, Wang YL, Chen S, Tsai HJ. Retina-specific cis-elements and binding nuclear proteins of carp rhodopsin gene. FEBS Lett. 2001;508:265–71. Hu CY, Yang CH, Chen WY, Huang CJ, Huang HY, Chen MS, et al. Egr1 gene knockdown affects embryonic ocular development in zebrafish. Mol Vis. 2006;12:1250–8. Huang HY, Dai ES, Liu JT, Tu CT, Yang TC, Tsai HJ. The embryonic expression patterns and the knockdown phenotypes of zebrafish ADP-ribosylation factor-like 6 interacting protein gene. Dev Dyn. 2009;238:232–40. Huang HY, Liu JT, Yan HY, Tsai HJ. Arl6ip1 plays a role in proliferation during zebrafish retinogenesis. Cells Tissues Organs. 2012;196:161–74. Tu CT, Yang TC, Huang HY, Tsai HJ. Zebrafish arl6ip1 is required for neural crest development during embryogenesis. PLoS One. 2012;7:e32899. Lin CY, Huang HY, Lu PN, Lin CW, Lu KM, Tsai HJ. Ras-related nuclear protein is required for late developmental stages of retinal cells in zebrafish eyes. Int J Dev Biol 2015;59:435–42. Lee HC, Chen YJ, Liu YW, Lin KY, Chen SW, Lin CY, et al. Transgenic zebrafish model to study translational control mediated by upstream open reading frame of human chop gene. Nucleic Acids Res. 2011;39:e139. Djuranovic S, Nahvi A, Green R. A parsimonious model for gene regulation by miRNAs. Science. 2011;331:550–3. Huntzinger E, Izaurralde E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet. 2011;12:99–110. Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 2010;79:351–79. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33. Rajewsky N. microRNA target predictions in animals. Nat Genet. 2006;38:S8–S13. Hsu RJ, Yang HJ, Tsai HJ. Labeled microRNA pull-down assay system: an experimental approach for high-throughput identification of microRNA-target mRNAs. Nucleic Acids Res. 2009;37:e77. Stahlhut C, Suárez Y, Lu J, Mishima Y, Giraldez AJ. miR-1 and miR-206 regulate angiogenesis by modulating VegfA expression in zebrafish. Development. 2012;139:4356–64. Lin CY, Lee HC, Fu CY, Ding YY, Chen JS, Lee MH, et al. MiR-1 and miR-206 target different genes to have opposing roles during angiogenesis in zebrafish embryos. Nat Commun. 2013;4:2829. Frith JE, Porrello ER, Cooper-White JJ. Concise review: new frontiers in microRNA-based tissue regeneration. Stem Cells Transl Med. 2014;3:969–76. Ujigo S, Kamei N, Hadoush H, Fujioka Y, Miyaki S, Nakasa T, et al. Administration of microRNA-210 promotes spinal cord regeneration in mice. Spine (Phila Pa 1976). 2014;39:1099–107. Porrello ER, Mahmoud AI, Simpson E, Johnson BA, Grinsfelder D, Canseco D, et al. Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family. Proc Natl Acad Sci U S A. 2013;110:187–92. Fuller-Carter PI, Carter KW, Anderson D, Harvey AR, Giles KM, Rodger J. Integrated analyses of zebrafish miRNA and mRNA expression profiles identify miR-29b and miR-223 as potential regulators of optic nerve regeneration. BMC Genomics. 2015;16:591. Traver D, Paw BH, Poss KD, Penberthy WT, Lin S, Zon LI. Transplantation and in vivo imaging of multilineage engraftment in zebrafish bloodless mutants. Nat Immunol. 2003;4:1238–46. Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008;132:631–44. Hsia N, Zon LI. Transcriptional regulation of hematopoietic stem cell development in zebrafish. Exp Hematol. 2005;33:1007–14. Weber GJ, Choe SE, Dooley KA, Paffett-Lugassy NN, Zhou Y, Zon LI. Mutant-specific gene programs in the zebrafish. Blood. 2005;106:521–30. North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord AM, et al. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature. 2007;447:1007–11. Goessling W, Allen RS, Guan X, Jin P, Uchida N, Dovey M, et al. Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models. Cell Stem Cell. 2011;8:445–58. Shin JT, Fishman MC. From Zebrafish to human: modular medical models. Annu Rev Genomics Hum Genet. 2002;3:311–40. Garrity DM, Childs S, Fishman MC. The heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome. Development. 2002;129:4635–45. Chen YH, Lee HC, Hsu RJ, Chen TY, Huang YK, Lo HC, et al. The toxic effect of Amiodarone on valve formation in the developing heart of zebrafish embryos. Reprod Toxicol. 2012;33:233–44. Lee HC, Lo HC, Lo DM, Su MY, Hu JR, Wu CC, et al. Amiodarone induces overexpression of similar to versican b to repress the EGFR/Gsk3b/Snail signaling axis during cardiac valve formation of zebrafish embryos. PloS One 2015;10:e0144751. Lee HC, Su MY, Lo HC, Wu CC, Hu JR, Lo DM, et al. Cancer metastasis and EGFR signaling is suppressed by Amiodarone-induced Versican V2. Oncotarget 2015;6:42976–87. Milan DJ, Jones IL, Ellinor PT, MacRae CA. In vivo recording of adult zebrafish electrocardiogram and assessment of drug-induced QT prolongation. Am J Physiol Heart Circ Physiol. 2006;291:H269–73. Arnaout R, Ferrer T, Huisken J, Spitzer K, Stainier DY, Tristani-Firouzi M, et al. Zebrafish model for human long QT syndrome. Proc Natl Acad Sci U S A. 2007;104:11316–21. Tsai CT, Wu CK, Chiang FT, Tseng CD, Lee JK, Yu CC, et al. In-vitro recording of adult zebrafish heart electrocardiogram - a platform for pharmacological testing. Clin Chim Acta. 2011;412:1963–7. Lu JW, Hsia Y, Tu HC, Hsiao YC, Yang WY, Wang HD, et al. Liver development and cancer formation in zebrafish. Birth Defects Res C Embryo Today. 2011;93:157–72. Feitsma H, Cuppen E. Zebrafish as a cancer model. Mol Cancer Res. 2008;6:685–94. Payne E, Look T. Zebrafish modelling of leukaemias. Br J Haematol. 2009;146:247–56. Stoletov K, Klemke R. Catch of the day: zebrafish as a human cancer model. Oncogene. 2008;27:4509–20. Amatruda JF, Shepard JL, Stern HM, Zon LI. Zebrafish as a cancer model system. Cancer Cell. 2002;1:229–31. Wang YH, Chen YH, Wu TN, Lin YJ, Tsai HJ. A keratin 18 transgenic zebrafish Tg(k18(2.9):RFP) treated with inorganic arsenite reveals visible overproliferation of epithelial cells. Toxicol Lett. 2006;163:191–7. Patton EE, Widlund HR, Kutok JL, Kopani KR, Amatruda JF, Murphey RD, et al. BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma. Curr Biol. 2005;15:249–54. Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3:453–8. Zhang B, Xuan C, Ji Y, Zhang W, Wang D. Zebrafish xenotransplantation as a tool for in vivo cancer study. Fam Cancer. 2015;14:487–93. Marques IJ, Weiss FU, Vlecken DH, Nitsche C, Bakkers J, Lagendijk AK, et al. Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model. BMC Cancer. 2009;9:128. Lal S, La Du J, Tanguay RL, Greenwood JA. Calpain 2 is required for the invasion of glioblastoma cells in the zebrafish brain microenvironment. J Neurosci Res. 2012;90:769–81. Zhao C, Yang H, Shi H, Wang X, Chen X, Yuan Y, et al. Distinct contributions of angiogenesis and vascular co-option during the initiation of primary microtumors and micrometastases. Carcinogenesis. 2011;32:1143–50. Stoletov K, Kato H, Zardouzian E, Kelber J, Yang J, Shattil S, et al. Visualizing extravasation dynamics of metastatic tumor cells. J Cell Sci. 2010;123:2332–41. Yang XJ, Cui W, Gu A, Xu C, Yu SC, Li TT, et al. A novel zebrafish xenotransplantation model for study of glioma stem cell invasion. PLoS One. 2013;8:e61801. Zhang B, Shimada Y, Kuroyanagi J, Umemoto N, Nishimura Y, Tanaka T. Quantitative phenotyping-based in vivo chemical screening in a zebrafish model of leukemia stem cell xenotransplantation. PLoS One. 2014;9:e85439. Shimada Y, Nishimura Y, Tanaka T. Zebrafish-based systems pharmacology of cancer metastasis. Methods Mol Biol. 2014;1165:223–38. Yeh JR, Munson KM, Elagib KE, Goldfarb AN, Sweetser DA, Peterson RT. Discovering chemical modifiers of oncogene-regulated hematopoietic differentiation. Nat Chem Biol. 2009;5:236–43. Small D, Levenstein M, Kim E, Carow C, Amin S, Rockwell P, et al. STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. Proc Natl Acad Sci U S A. 1994;91:459–63. He BL, Shi X, Man CH, Ma AC, Ekker SC, Chow HC, et al. Functions of flt3 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia. Blood. 2014;123:2518–29. Gross S, Cairns RA, Minden MD, Driggers EM, Bittinger MA, Jang HG, et al. Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med. 2010;207:339–44. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011;11:85–95. Shi X, He BL, Ma AC, Guo Y, Chi Y, Man CH, et al. Functions of idh1 and its mutation in the regulation of developmental hematopoiesis in zebrafish. Blood. 2015;125:2974–84. Li Z, Huang X, Zhan H, Zeng Z, Li C, Spitsbergen JM, et al. Inducible and repressable oncogene-addicted hepatocellular carcinoma in Tet-on xmrk transgenic zebrafish. J Hepatol. 2012;56:419–25. Nguyen AT, Emelyanov A, Koh CH, Spitsbergen JM, Parinov S, Gong Z. An inducible kras (V12) transgenic zebrafish model for liver tumorigenesis and chemical drug screening. Dis Model Mech. 2012;5:63–72. Li Z, Zheng W, Wang Z, Zeng Z, Zhan H, Li C, et al. A transgenic zebrafish liver tumor model with inducible Myc expression reveals conserved Myc signatures with mammalian liver tumors. Dis Model Mech. 2013;6:414–23. Zheng W, Li Z, Nguyen AT, Li C, Emelyanov A, Gong Z. Xmrk, kras and myc transgenic zebrafish liver cancer models share molecular signatures with subsets of human hepatocellular carcinoma. PLoS One. 2014;9, e91179. Kalueff AV, Echevarria DJ, Stewart AM. Gaining translational momentum: more zebrafish models for neuroscience research. Prog Neuropsychopharmacol Biol Psychiatry. 2014;55:1–6. Kalueff AV, Stewart AM, Gerlai R. Zebrafish as an emerging model for studying complex brain disorders. Trends Pharmacol Sci. 2014;35:63–75. Stewart AM, Braubach O, Spitsbergen J, Gerlai R, Kalueff AV. Zebrafish models for translational neuroscience research: from tank to bedside. Trends Neurosci. 2014;37:264–78. Fonseka TM, Wen XY, Foster JA, Kennedy SH. Zebrafish models of major depressive disorders. J Neurosci Res. 2016;94:3–14. Cachat J, Stewart A, Utterback E, Hart P, Gaikwad S, Wong K, et al. Three-dimensional neurophenotyping of adult zebrafish behavior. PLoS One. 2011;6:e17597. Nguyen M, Stewart AM, Kalueff AV. Aquatic blues: modeling depression and antidepressant action in zebrafish. Prog Neuropsychopharmacol Biol Psychiatry. 2014;55:26–39. Teles MC, Dahlbom SJ, Winberg S, Oliveira RF. Social modulation of brain monoamine levels in zebrafish. Behav Brain Res. 2013;253:17–24. Karnik I, Gerlai R. Can zebrafish learn spatial tasks? An empirical analysis of place and single CS-US associative learning. Behav Brain Res. 2012;233:415–21. Carvalho AF, Miskowiak KK, Hyphantis TN, Kohler CA, Alves GS, Bortolato B, et al. Cognitive dysfunction in depression-pathophysiology and novel targets. CNS Neurol Disord Drug Targets. 2014;13:1819–35. Ellis LD, Soanes KH. A larval zebrafish model of bipolar disorder as a screening platform for neuro-therapeutics. Behav Brain Res. 2012;233:450–7. Maximino C, Puty B, Benzecry R, Araújo J, Lima MG, De Jesus Oliveira Batista E, et al. Role of serotonin in zebrafish (Danio rerio) anxiety: relationship with serotonin levels and effect of buspirone, WAY 100635, SB 224289, fluoxetine and para-chlorophenylalanine (pCPA) in two behavioral models. Neuropharmacology. 2013;71:83–97. Ziv L, Muto A, Schoonheim PJ, Meijsing SH, Strasser D, Ingraham HA, et al. An affective disorder in zebrafish with mutation of the glucocorticoid receptor. Mol Psychiatry. 2013;18:681–91. Schwarzenbach RP, Egli T, Hofstetter TB, Von Gunten U, Wehrli B. Global Water Pollution and Human Health. Annu Rev Env Resour. 2010;35:109–36. Amanuma K, Takeda H, Amanuma H, Aoki Y. Transgenic zebrafish for detecting mutations caused by compounds in aquatic environments. Nat Biotechnol. 2000;18:62–5. Amanuma K, Tone S, Saito H, Shigeoka T, Aoki Y. Mutational spectra of benzo [a] pyrene and MeIQx in rpsL transgenic zebrafish embryos. Mutat Res. 2002;513:83–92. Chen T, Lu JK. Transgenic fish technology: basic principles and their application in basic and applied research. In: De la Fuente J, Castro FO, editors. Gene Transfer in Aquatic Organism. Berlin: Springer; 1998; p. 45–73. Ng GH, Gong Z. GFP transgenic medaka (Oryzias latipes) under the inducible cyp1a promoter provide a sensitive and convenient biological indicator for the presence of TCDD and other persistent organic chemicals. PLoS One. 2013;8:e64334. Lee HC, Lu PN, Huang HL, Chu C, Li HP, Tsai HJ. Zebrafish transgenic line huORFZ is an effective living bioindicator for detecting environmental toxicants. PLoS One. 2014;9:e90160. Xu H, Li C, Li Y, Ng GH, Liu C, Zhang X, et al. Generation of Tg (cyp1a:gfp) transgenic zebrafish for development of a convenient and sensitive in vivo assay for aryl hydrocarbon receptor activity. Mar Biotechnol (NY). 2015;17:831–40.