Addressing the Genetics of Human Mental Health Disorders in Model Organisms

Annual Review of Genomics and Human Genetics

Volumn 16, Issue , 2015, Pages 173-197

  McCammon, Jasmine M ^a   Sive, Hazel ^a,b  

^a WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Autism; Psychiatric disorders; Schizophrenia; Zebrafish

Indexed keywords

DEXAMETHASONE; FLUDROXYCORTIDE; LEFLUNOMIDE;

ARTICLE; BEHAVIOR; CAENORHABDITIS ELEGANS; COMORBIDITY; CYTOPLASM; DROSOPHILA MELANOGASTER; DRUG DEVELOPMENT; DRUG INDUSTRY; GENE FUNCTION; GENE INTERACTION; GENETIC ASSOCIATION; GENETIC LINKAGE; GENETIC MANIPULATION; GENETIC VARIABILITY; HUMAN; HUMAN GENETICS; MAMMAL CELL; MENTAL DISEASE; MOLECULAR PATHOLOGY; MOLLUSC; MOUSE MODEL; NERVE CELL CULTURE; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHENOTYPE; PLURIPOTENT STEM CELL; RNA INTERFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; XENOPUS LAEVIS; ZEBRA FISH; ANIMAL; ANIMAL BEHAVIOR; APLYSIA; CELL CULTURE; DISEASE MODEL; GENE EXPRESSION REGULATION; GENETICS; MENTAL DISORDERS; MOUSE; NERVE CELL; PATHOLOGY; PHYSIOLOGY; PRECLINICAL STUDY; PROCEDURES;

ANIMALS; APLYSIA; BEHAVIOR, ANIMAL; CAENORHABDITIS ELEGANS; CELLS, CULTURED; DISEASE MODELS, ANIMAL; DROSOPHILA MELANOGASTER; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; GENE EXPRESSION REGULATION; HUMANS; MENTAL DISORDERS; MICE; NEURONS; PLURIPOTENT STEM CELLS; XENOPUS LAEVIS; ZEBRAFISH;

EID: 84940647911     PISSN: 15278204     EISSN: 1545293X     Source Type: Book Series    
DOI: 10.1146/annurev-genom-090314-050048     Document Type: Article

References (183)

1. Abbott A. 2011. Novartis to shut brain research facility. Nature 480:161-62
2. Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, et al. 2000. The genome sequence of Drosophila melanogaster. Science 287:2185-95
3. Amir RE, Van den Veyver IB,Wan M, Tran CQ, Francke U, Zoghbi HY. 1999. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 Nat. Genet. 23:185-88
4. Amsterdam A, Hopkins N. 2006. Mutagenesis strategies in zebrafish for identifying genes involved in development and disease. Trends Genet. 22:473-78
5. Anderson G, Maes M. 2012. Melatonin: an overlooked factor in schizophrenia and in the inhibition of anti-psychotic side effects. Metab. Brain Dis. 27:113-19
6. Arnedo J, Svrakic DM, Del Val C, Romero-Zaliz R, Hernández-Cuervo H, et al. 2015. Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies. Am. J. Psychiatry 172:139-53
7. AsaiA, SahaniN,KanekiM,Ouchi Y, Martyn JA, Yasuhara SE. 2007. Primary role of functional ischemia, quantitative evidence for the two-hit mechanism, and phosphodiesterase-5 inhibitor therapy in mouse muscular dystrophy. PLOS ONE 2:e806
8. Asakawa K, Kawakami K. 2008. Targeted gene expression by the Gal4-UAS system in zebrafish. Dev. Growth Differ. 50:391-99
9. Bai X, Kim J, Yang Z, Jurynec MJ, Akie TE, et al. 2010. TIF1γcontrols erythroid cell fate by regulating transcription elongation. Cell 142:133-43
10. Bernier R, Golzio C, Xiong B, Stessman HA, Coe BP, et al. 2014. Disruptive CHD8 mutations define a subtype of autism early in development. Cell 158:263-76
11. Bittencourt J, Velasques B, Teixeira S, Basile LF, Salles JI, et al. 2013. Saccadic eye movement applications for psychiatric disorders. Neuropsychiatr. Dis. Treat. 9:1393-409
12. Blaker-Lee A, Gupta S, McCammon JM, De Rienzo G, Sive H. 2012. Zebrafish homologs of genes within 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes. Dis. Models Mech. 5:834-51
13. BlankM,Guerim LD, Cordeiro RF, Vianna MR. 2009. A one-trial inhibitory avoidance task to zebrafish: rapid acquisition of an NMDA-dependent long-term memory. Neurobiol. Learn. Mem. 92:529-34
14. Bozdagi O, Sakurai T, Papapetrou D, Wang X, Dickstein DL, et al. 2010. Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol. Autism 1:15
15. Bozdagi O, Tavassoli T, Buxbaum JD. 2013. Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay. Mol. Autism 4:9
16. Brady RO Jr.,McCarthy JM, Prescot AP, Jensen JE, Cooper AJ, et al. 2013. Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder. Bipolar Disord. 15:434-39
17. Brenman JE, Chao DS, Xia H, Aldape K, Bredt DS. 1995. Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell 82:743-52
18. Brennan CH. 2011. Zebrafish behavioural assays of translational relevance for the study of psychiatric disease. Rev. Neurosci. 22:37-48
19. Brennand KJ, Landek-Salgado MA, Sawa A. 2014. Modeling heterogeneous patients with a clinical diagnosis of schizophrenia with induced pluripotent stem cells. Biol. Psychiatry 75:936-44
20. Brennand KJ, Savas JN, Kim Y, Tran N, Simone A, et al. 2015. Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia. Mol. Psychiatry 20:361-68
21. Brockschmidt A, Filippi A, Charbel Issa P, Nelles M, Urbach H, et al. 2011. Neurologic and ocular phenotype in Pitt-Hopkins syndrome and a zebrafish model. Hum. Genet. 130:645-55
22. Burguiere A, De Bundel D, Valjent E, Roger J, Smolders I, et al. 2013. Combination of group I mGlu receptors antagonist with dopaminergic agonists strengthens the synaptic transmission at corticostriatal synapses in culture. Neuropharmacology 66:151-57
23. BuskeC,Gerlai R. 2012. Maturation of shoaling behavior is accompanied by changes in the dopaminergic and serotoninergic systems in zebrafish. Dev. Psychobiol. 54:28-35
24. C. elegans Seq. Consort. 1998. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282:2012-18
25. Cachat J, Stewart A, Grossman L, Gaikwad S, Kadri F, et al. 2010. Measuring behavioral and endocrine responses to novelty stress in adult zebrafish. Nat. Protoc. 5:1786-99
26. Cavarec L, Vincent L, Le Borgne C, Plusquellec C, Ollivier N, et al. 2013. In vitro screening for drug-induced depression and/or suicidal adverse effects: a new toxicogenomic assay based on CE-SSCP analysis of HTR2C mRNA editing in SH-SY5Y cells. Neurotox. Res. 23:49-62
27. Chadman KK, Gong S, Scattoni ML, Boltuck SE, Gandhy SU, et al. 2008. Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. Autism Res. 1:147-58
28. Chen J, Lin M, Foxe JJ, Pedrosa E, Hrabovsky A, et al. 2013. Transcriptome comparison of human neurons generated using induced pluripotent stem cells derived from dental pulp and skin fibroblasts. PLOS ONE 8:e75682
29. Chen RZ, Akbarian S, Tudor M, Jaenisch R. 2001. Deficiency ofmethyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat. Genet. 27:327-31
30. Choi YB, Li HL, Kassabov SR, Jin I, Puthanveettil SV, et al. 2011. Neurexin-neuroligin transsynaptic interaction mediates learning-related synaptic remodeling and long-term facilitation in Aplysia. Neuron 70:468-81
31. Cocchiaro JL, Rawls JF. 2013. Microgavage of zebrafish larvae. J. Vis. Exp. 72:e4434
32. Coghlan S, Horder J, Inkster B, Mendez MA, Murphy DG, Nutt DJ. 2012. GABA system dysfunction in autism and related disorders: from synapse to symptoms. Neurosci. Biobehav. Rev. 36:2044-55
33. Crawley JN. 2012. Translational animal models of autism and neurodevelopmental disorders. Dialogues Clin. Neurosci. 14:293-305
34. Cross-Disorder Group Psychiatr. Genomics Consort. 2013. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381:1371-79
35. Culetto E, Sattelle DB. 2000. A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes. Hum. Mol. Genet. 9:869-77
36. Cutler C, Multani P, Robbins D, Kim HT, Le T, et al. 2013. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood 122:3074-81
37. Dash PK, Hochner B, Kandel ER. 1990. Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation. Nature 345:718-21
38. De Rienzo G, Bishop JA, Mao Y, Pan L, Ma TP, et al. 2011. Disc1 regulates both β-catenin-mediated and noncanonical Wnt signaling during vertebrate embryogenesis. FASEB J. 25:4184-97
39. De Rienzo G, Gutzman JH, Sive H. 2012. Efficient shRNA-mediated inhibition of gene expression in zebrafish. Zebrafish 9:97-107
40. DiBella LM, Park A, Sun Z. 2009. Zebrafish Tsc1 reveals functional interactions between the cilium and the TOR pathway. Hum. Mol. Genet. 18:595-606
41. Dolen G, Osterweil E, Rao BS, Smith GB, Auerbach BD, et al. 2007. Correction of fragile X syndrome in mice. Neuron 56:955-62
42. Drapeau E, Dorr NP, Elder GA, Buxbaum JD. 2014. Absence of strong strain effects in behavioral analyses of Shank3-deficient mice. Dis. Models Mech. 7:667-81
43. Drerup CM, Wiora HM, Topczewski J, Morris JA. 2009. Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation. Development 136:2623-32
44. Dueck A, Thome J, Haessler F. 2012. The role of sleep problems and circadian clock genes in childhood psychiatric disorders. J. Neural Transm. 119:1097-104
45. Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, et al. 2007. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat. Genet. 39:25-27
46. Dykens EM, Sutcliffe JS, Levitt P. 2004. Autism and 15q11-q13 disorders: behavioral, genetic, and pathophysiological issues. Ment. Retard. Dev. Disabil. Res. Rev. 10:284-91
47. Edwards D, StancescuM,Molnar P, Hickman JJ. 2013. Two cell circuits of oriented adult hippocampal neurons on self-assembled monolayers for use in the study of neuronal communication in a defined system. ACS Chem. Neurosci. 4:1174-82
48. Elbaz I, Foulkes NS, Gothilf Y, Appelbaum L. 2013. Circadian clocks, rhythmic synaptic plasticity and the sleep-wake cycle in zebrafish. Front. Neural Circ. 7:9
49. Elsen GE, Choi LY, Prince VE, Ho RK. 2009. The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration. Dev. Biol. 335:78-92
50. Ermolaeva MA, Schumacher B. 2014. Insights from the worm: the C. elegans model for innate immunity. Semin. Immunol. 26:303-9
51. Fajardo O, Zhu P, Friedrich RW. 2013. Control of a specific motor program by a small brain area in zebrafish. Front. Neural Circ. 7:67
52. Flint J, Timpson N, Munafo M. 2014. Assessing the utility of intermediate phenotypes for genetic mapping of psychiatric disease. Trends Neurosci. 37:733-41
53. Gabriele S, Sacco R, Persico AM. 2014. Blood serotonin levels in autism spectrum disorder: a systematic review and meta-analysis. Eur. Neuropsychopharmacol. 24:919-29
54. Gauthier J, Champagne N, Lafreniere RG, Xiong L, Spiegelman D, et al. 2010. De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. PNAS 107:7863-68
55. Gibbs EM, Horstick EJ, Dowling JJ. 2013. Swimming into prominence: the zebrafish as a valuable tool for studying human myopathies and muscular dystrophies. FEBS J. 280:4187-97
56. GoesslingW, Allen RS, Guan X, Jin P, Uchida N, et al. 2011. Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models. Cell Stem Cell 8:445-58
57. Golzio C, Willer J, Talkowski ME, Oh EC, Taniguchi Y, et al. 2012. KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant. Nature 485:363-67
58. Grunblatt E, Bartl J, Marinova Z, Walitza S. 2013. In vitro study methodologies to investigate genetic aspects and effects of drugs used in attention-deficit hyperactivity disorder. J. Neural Transm. 120:131-39
59. Guy J, Hendrich B, Holmes M, Martin JE, Bird A. 2001. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat. Genet. 27:322-26
60. Hallcher LM, Sherman WR. 1980. The effects of lithium ion and other agents on the activity of myoinositol-1-phosphatase from bovine brain. J. Biol. Chem. 255:10896-901
61. Hamdani N, Doukhan R, Kurtlucan O, Tamouza R, Leboyer M. 2013. Immunity, inflammation, and bipolar disorder: diagnostic and therapeutic implications. Curr. Psychiatry Rep. 15:387
62. Hao J, Ao A, Zhou L, Murphy CK, Frist AY, et al. 2013. Selective small molecule targeting β-catenin function discovered by in vivo chemical genetic screen. Cell Rep. 4:898-904
63. Hashimoto M, Hibi M. 2012. Development and evolution of cerebellar neural circuits. Dev. Growth Differ. 54:373-89
64. Hayashi-Takagi A, Araki Y,NakamuraM,Vollrath B,Duron SG, et al. 2014. PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence. PNAS 111:6461-66
65. He X, Saint-Jeannet JP, Woodgett JR, Varmus HE, Dawid IB. 1995. Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos. Nature 374:617-22
66. Helenius IT, Yeh JR. 2012. Small zebrafish in a big chemical pond. J. Cell. Biochem. 113:2208-16
67. Hisano Y, Ota S, Kawahara A. 2014. Genome editing using artificial site-specific nucleases in zebrafish. Dev. Growth Differ. 56:26-33
68. Hodgkin AL,Huxley AF. 1939. Action potentials recorded from inside a nerve fibre. Nature 144:710-11
69. Howe K, ClarkMD, Torroja CF, Torrance J, Berthelot C, et al. 2013. The zebrafish reference genome sequence and its relationship to the human genome. Nature 496:498-503
70. Huber KM, Gallagher SM, Warren ST, Bear MF. 2002. Altered synaptic plasticity in a mouse model of fragile X mental retardation. PNAS 99:7746-50
71. Hunt PR, Olejnik N, Sprando RL. 2012. Toxicity ranking of heavy metals with screening method using adult Caenorhabditis elegans and propidium iodide replicates toxicity ranking in rat. Food Chem. Toxicol. 50:3280-90
72. Jacquemont S, Curie A, des Portes V, TorrioliMG, Berry-Kravis E, et al. 2011. Epigenetic modification of the FMR1 gene in fragileXsyndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci. Transl. Med. 3:64ra1
73. Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, et al. 2003. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat. Genet. 34:27-29
74. Kaitin KI, Milne CP. 2011. A dearth of new meds. Sci. Am. 305:16
75. Kao KR, Masui Y, Elinson RP. 1986. Lithium-induced respecification of pattern in Xenopus laevis embryos. Nature 322:371-73
76. Kawahara G, Karpf JA, Myers JA, Alexander MS, Guyon JR, Kunkel LM. 2011. Drug screening in a zebrafish model of Duchenne muscular dystrophy. PNAS 108:5331-36
77. Kendler KS. 2013. What psychiatric genetics has taught us about the nature of psychiatric illness and what is left to learn. Mol. Psychiatry 18:1058-66
78. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR,Walters EE. 2005. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 62:593-602
79. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. 2005. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 62:617-27
80. Kettleborough RN, Busch-Nentwich EM,Harvey SA,Dooley CM, de Bruijn E, et al. 2013. A systematic genome-wide analysis of zebrafish protein-coding gene function. Nature 496:494-97
81. Khan KH, Blanco-Codesido M, Molife LR. 2014. Cancer therapeutics: targeting the apoptotic pathway. Crit. Rev. Oncol. Hematol. 90:200-19
82. Kim HG, Kishikawa S, Higgins AW, Seong IS, Donovan DJ, et al. 2008. Disruption of neurexin 1 associated with autism spectrum disorder. Am. J. Hum. Genet. 82:199-207
83. Kim SH, Speirs CK, Solnica-Krezel L, Ess KC. 2011. Zebrafish model of tuberous sclerosis complex reveals cell-autonomous and non-cell-autonomous functions ofmutant tuberin. Dis. Models Mech. 4:255-67
84. Kimura Y, Satou C, Fujioka S, Shoji W, Umeda K, et al. 2013. Hindbrain V2a neurons in the excitation of spinal locomotor circuits during zebrafish swimming. Curr. Biol. 23:843-49
85. Klein PS, Melton DA. 1996. A molecular mechanism for the effect of lithium on development. PNAS 93:8455-59
86. Kohane IS, McMurry A, Weber G, MacFadden D, Rappaport L, et al. 2012. The co-morbidity burden of children and young adults with autism spectrum disorders. PLOS ONE 7:e33224
87. Kokel D, Bryan J, Laggner C, White R, Cheung CY, et al. 2010. Rapid behavior-based identification of neuroactive small molecules in the zebrafish. Nat. Chem. Biol. 6:231-37
88. Konopka RJ, Benzer S. 1971. Clock mutants of Drosophila melanogaster. PNAS 68:2112-16
89. Lancaster MA, Knoblich JA. 2014. Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345:1247125
90. Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, et al. 2013. Cerebral organoids model human brain development and microcephaly. Nature 501:373-79
91. Lindor NM, McMaster ML, Lindor CJ, Greene MH. 2008. Concise handbook of familial cancer susceptibility syndromes-second edition. J. Natl. Cancer Inst. Monogr. 2008:3-93
92. Lindsay EA, MorrisMA, Gos A, Nestadt G, Wolyniec PS, et al. 1995. Schizophrenia and chromosomal deletions within 22q11.2. Am. J. Hum. Genet. 56:1502-3
93. Lord C, Petkova E, Hus V, Gan W, Lu F, et al. 2012. A multisite study of the clinical diagnosis of different autism spectrum disorders. Arch. Gen. Psychiatry 69:306-13
94. M'Hamdi O, Ouertani I, Chaabouni-Bouhamed H. 2014. Update on the genetics of Bardet-Biedl syndrome. Mol. Syndromol. 5:51-56
95. Maaswinkel H, Zhu L, Weng W. 2013. Assessing social engagement in heterogeneous groups of zebrafish: a new paradigm for autism-like behavioral responses. PLOS ONE 8:e75955
96. Malhotra D, Sebat J. 2012. CNVs: harbingers of a rare variant revolution in psychiatric genetics. Cell 148:1223-41
97. Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, et al. 2010. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143:527-39
98. Martin EA, Barresi R, Byrne BJ, Tsimerinov EI, Scott BL, et al. 2012. Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy. Sci. Transl. Med. 4:162ra55
99. Maximino C, de Brito TM, da Silva Batista AW, Herculano AM, Morato S, Gouveia A Jr. 2010. Measuring anxiety in zebrafish: a critical review. Behav. Brain Res. 214:157-71
100. McBride SM, Choi CH,WangY,Liebelt D, Braunstein E, et al. 2005. Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron 45:753-64
101. McLaren D, Gorba T, Marguerie de Rotrou A, Pillai G, Chappell C, et al. 2013. Automated large-scale culture and medium-throughput chemical screen for modulators of proliferation and viability of human induced pluripotent stem cell-derived neuroepithelial-like stem cells. J. Biomol. Screen. 18:258-68
102. McMahon AP, Moon RT. 1989. Ectopic expression of the proto-oncogene int-1 in Xenopus embryos leads to duplication of the embryonic axis. Cell 58:1075-84
103. Merikangas KR,He JP, Burstein M, Swanson SA, Avenevoli S, et al. 2010. Lifetime prevalence ofmental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A). J. Am. Acad. Child Adolesc. Psychiatry 49:980-89
104. Miller G. 2010. Is pharma running out of brainy ideas? Science 329:502-4
105. Moretti P, Bouwknecht JA, Teague R, Paylor R, Zoghbi HY. 2005. Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome. Hum. Mol. Genet. 14:205-20
106. Mouse Genome Seq. Consort. 2002. Initial sequencing and comparative analysis of the mouse genome. Nature 420:520-62
107. Mukai J,Dhilla A, Drew LJ, Stark KL,Cao L, et al. 2008. Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion. Nat. Neurosci. 11:1302-10
108. Nakatani J, Tamada K, Hatanaka F, Ise S, Ohta H, et al. 2009. Abnormal behavior in a chromosomeengineered mouse model for human 15q11-13 duplication seen in autism. Cell 137:1235-46
109. Nasevicius A, Ekker SC. 2000. Effective targeted gene "knockdown" in zebrafish. Nat. Genet. 26:216-20
110. Neill JC, Barnes S, Cook S, Grayson B, Idris NF, et al. 2010. Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus onNMDAreceptor antagonism. Pharmacol. Ther. 128:419-32
111. Nelson MD, Rader F, Tang X, Tavyev J, Nelson SF, et al. 2014. PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy. Neurology 82:2085-91
112. Ng MC, Yang YL, Lu KT. 2013. Behavioral and synaptic circuit features in a zebrafish model of fragile X syndrome. PLOS ONE 8:e51456
113. North TE, GoesslingW,Walkley CR, Lengerke C, Kopani KR, et al. 2007. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 447:1007-11
114. O'Brien WT, Klein PS. 2009. ValidatingGSK3 as an in vivo target of lithium action. Biochem. Soc. Trans. 37:1133-38
115. Panula P, Chen YC, Priyadarshini M, Kudo H, Semenova S, et al. 2010. The comparative neuroanatomy and neurochemistry of zebrafishCNSsystems of relevance to human neuropsychiatric diseases. Neurobiol. Dis. 40:46-57
116. Pariante CM. 2009. Risk factors for development of depression and psychosis: glucocorticoid receptors and pituitary implications for treatment with antidepressant and glucocorticoids. Ann. N.Y. Acad. Sci. 1179:144-52
117. Pasca SP, Portmann T, Voineagu I, YazawaM, Shcheglovitov A, et al. 2011. Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat. Med. 17:1657-62
118. Patel JN, McLeod HL, Innocenti F. 2013. Implications of genome-wide association studies in cancer therapeutics. Br. J. Clin. Pharmacol. 76:370-80
119. Peal DS,Mills RW, Lynch SN,Mosley JM, Lim E, et al. 2011. Novel chemical suppressors of long QT syndrome identified by an in vivo functional screen. Circulation 123:23-30
120. Peca J, Feliciano C, Ting JT, Wang W, Wells MF, et al. 2011. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472:437-42
121. Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RC, et al. 1995. Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376:348-51
122. Pietri T, Roman AC, Guyon N, Romano SA, Washbourne P, et al. 2013. The first mecp2-null zebrafish model shows altered motor behaviors. Front. Neural Circuits 7:118
123. Pinto D, Delaby E,Merico D, BarbosaM,Merikangas A, et al. 2014. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am. J. Hum. Genet. 94:677-94
124. Poon KL, Brand T. 2013. The zebrafish model system in cardiovascular research: a tiny fish with mighty prospects. Glob. Cardiol. Sci. Pract. 2013:9-28
125. Prilutsky D, Palmer NP, Smedemark-Margulies N, Schlaeger TM, Margulies DM, Kohane IS. 2014. iPSC-derived neurons as a higher-throughput readout for autism: promises and pitfalls. Trends Mol. Med. 20:91-104
126. Ramachandran KV, Hennessey JA, Barnett AS, Yin X, Stadt HA, et al. 2013. Calcium influx through L-type CaV1.2 Ca2+ channels regulates mandibular development. J. Clin. Investig. 123:1638-46
127. Randall FE, Garcia-Munoz M, Vickers C, Schock SC, Staines WA, Arbuthnott GW. 2011. The corticostriatal system in dissociated cell culture. Front. Syst. Neurosci. 5:52
128. Ranga A,Gjorevski N, LutolfMP. 2014. Drug discovery through stem cell-based organoidmodels. Adv. Drug Deliv. Rev. 69-70C:19-28
129. Rayport SG, Schacher S. 1986. Synaptic plasticity in vitro: cell culture of identified Aplysia neurons mediating short-term habituation and sensitization. J. Neurosci. 6:759-63
130. Reeber SL, Otis TS, Sillitoe RV. 2013. New roles for the cerebellum in health and disease. Front. Syst. Neurosci. 7:83
131. Reiter LT, Potocki L, Chien S, Gribskov M, Bier E. 2001. A systematic analysis of human diseaseassociated gene sequences in Drosophila melanogaster. Genome Res. 11:1114-25
132. Renshaw SA, Trede NS. 2012. A model 450 million years in the making: zebrafish and vertebrate immunity. Dis. Models Mech. 5:38-47
133. Rihel J, Prober DA, Arvanites A, Lam K, Zimmerman S, et al. 2010. Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation. Science 327:348-51
134. Rizak J, Tan H, Zhu H, Wang JF. 2014. Chronic treatment with the mood stabilizing drug lithium upregulates nuclear factor E2-related factor 2 in rat pheochromocytoma PC12 cells in vitro. Neuroscience 256:223-29
135. Robu ME, Larson JD, Nasevicius A, Beiraghi S, Brenner C, et al. 2007. p53 activation by knockdown technologies. PLOS Genet. 3:e78
136. Rossignol DA, Frye RE. 2011. Melatonin in autism spectrum disorders: a systematic review and metaanalysis. Dev. Med. Child Neurol. 53:783-92
137. Saur T, DeMarco SE, Ortiz A, Sliwoski GR, Hao L, et al. 2013. A genome-wide RNAi screen in Caenorhabditis elegans identifies the nicotinic acetylcholine receptor subunit ACR-7 as an antipsychotic drug target. PLOS Genet. 9:e1003313
138. Schaz U, Fohr KJ, Liebau S, Fulda S, Koelch M, et al. 2011. Dose-dependent modulation of apoptotic processes by fluoxetine in maturing neuronal cells: an in vitro study. World J. Biol. Psychiatry 12:89-98
139. Schizophr. Work. Group Psychiatr. Genomics Consort. 2014. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511:421-27
140. Schmold N, Syed NI. 2012. Molluscan neurons in culture: shedding light on synapse formation and plasticity. J. Mol. Histol. 43:383-99
141. Schoonheim PJ, Arrenberg AB, Del Bene F, Baier H. 2010. Optogenetic localization and genetic perturbation of saccade-generating neurons in zebrafish. J. Neurosci. 30:7111-20
142. Scott EK, Mason L, Arrenberg AB, Ziv L, Gosse NJ, et al. 2007. Targeting neural circuitry in zebrafish using GAL4 enhancer trapping. Nat. Methods 4:323-26
143. Shcheglovitov A, Shcheglovitova O, Yazawa M, Portmann T, Shu R, et al. 2013. SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. Nature 503:267-71
144. Shepherd I, Eisen J. 2011. Development of the zebrafish enteric nervous system. Methods Cell Biol. 101:143-60
145. Shih DF, Hsiao CD, Min MY, Lai WS, Yang CW, et al. 2013. Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions. PLOS ONE 8:e71741
146. Siegfried E, Wilder EL, Perrimon N. 1994. Components of wingless signalling in Drosophila. Nature 367:76-80
147. Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. 2008. Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a populationderived sample. J. Am. Acad. Child Adolesc. Psychiatry 47:921-29
148. Singh KK, De Rienzo G, Drane L,Mao Y, Flood Z, et al. 2011. Common DISC1 polymorphisms disrupt Wnt/GSK3βsignaling and brain development. Neuron 72:545-58
149. Sive H. 2011. "Model" or "tool"? New definitions for translational research. Dis. Models Mech. 4:137-38
150. Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, et al. 2011. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470:105-9
151. Stan AD, Lewis DA. 2012. Altered cortical GABA neurotransmission in schizophrenia: insights into novel therapeutic strategies. Curr. Pharm. Biotechnol. 13:1557-62
152. Stark KL, Xu B, Bagchi A, LaiWS, Liu H, et al. 2008. Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nat. Genet. 40:751-60
153. Stewart AM, Nguyen M, Wong K, Poudel MK, Kalueff AV. 2014. Developing zebrafish models of autism spectrum disorder (ASD). Prog. Neuro-Psychopharmacol. Biol. Psychiatry 50:27-36
154. Sullivan PF,Daly MJ,O'Donovan M. 2012. Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nat. Rev. Genet. 13:537-51
155. Sulston JE, Horvitz HR. 1977. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev. Biol. 56:110-56
156. Tabuchi K, Blundell J, EthertonMR,HammerRE, LiuX, et al. 2007.Aneuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318:71-76
157. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, et al. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861-72
158. Takebe T, Sekine K, EnomuraM, Koike H, Kimura M, et al. 2013. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499:481-84
159. TayehMK, Yen HJ, Beck JS, Searby CC, Westfall TA, et al. 2008. Genetic interaction between Bardet-Biedl syndrome genes and implications for limb patterning. Hum. Mol. Genet. 17:1956-67
160. Thomas KR,CapecchiMR. 1987. Site-directedmutagenesis by gene targeting inmouse embryo-derived stem cells. Cell 51:503-12
161. Tian LJ, Cao JH, Deng XQ, Zhang CL, Qian T, et al. 2014. Gene expression profiling of Duchenne muscular dystrophy reveals characteristics along disease progression. Genet. Mol. Res. 13:1402-11
162. Toma C, Hervas A, Balmana N, Salgado M, Maristany M, et al. 2013. Neurotransmitter systems and neurotrophic factors in autism: association study of 37 genes suggests involvement of DDC. World J. Biol. Psychiatry 14:516-27
163. Trillenberg P, Lencer R, Heide W. 2004. Eye movements and psychiatric disease. Curr. Opin. Neurol. 17:43-47
164. Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, et al. 2009. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. PNAS 106:2029-34
165. Vashlishan AB, Madison JM, Dybbs M, Bai J, Sieburth D, et al. 2008. An RNAi screen identifies genes that regulate GABA synapses. Neuron 58:346-61
166. Voas MG, Glenn TD, Raphael AR, Talbot WS. 2009. Schwann cells inhibit ectopic clustering of axonal sodium channels. J. Neurosci. 29:14408-14
167. Voleti B, Duman RS. 2012. The roles of neurotrophic factor and Wnt signaling in depression. Clin. Pharmacol. Ther. 91:333-38
168. Wang X, McCoy PA, Rodriguiz RM, Pan Y, Je HS, et al. 2011. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum. Mol. Genet. 20:3093-108
169. Wartha K, Herting F, Hasmann M. 2014. Fit-for purpose use of mouse models to improve predictivity of cancer therapeutics evaluation. Pharmacol. Ther. 142:351-61
170. Weger BD, Weger M, Nusser M, Brenner-Weiss G, Dickmeis T. 2012. A chemical screening system for glucocorticoid stress hormone signaling in an intact vertebrate. ACS Chem. Biol. 7:1178-83
171. White JG, Southgate E, Thomson JN, Brenner S. 1986. The structure of the nervous system of the nematode Caenorhabditis elegans. Philos. Trans. R. Soc. Lond. B 314:1-340
172. White RM, Cech J, Ratanasirintrawoot S, Lin CY, Rahl PB, et al. 2011. DHODH modulates transcriptional elongation in the neural crest and melanoma. Nature 471:518-22
173. White RM, Rose K, Zon L. 2013. Zebrafish cancer: the state of the art and the path forward. Nat. Rev. Cancer 13:624-36
174. Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, et al. 2013. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet 382:1575-86
175. Wolman MA, Jain RA, Liss L, Granato M. 2011. Chemical modulation of memory formation in larval zebrafish. PNAS 108:15468-73
176. Woods IG, Kelly PD, Chu F, Ngo-Hazelett P, Yan YL, et al. 2000. A comparative map of the zebrafish genome. Genome Res. 10:1903-14
177. Wray NR, Lee SH, Mehta D, Vinkhuyzen AA, Dudbridge F, Middeldorp CM. 2014. Research review: polygenic methods and their application to psychiatric traits. J. Child Psychol. Psychiatry 55:1068-87
178. Wyart C, Del Bene F,Warp E, Scott EK,Trauner D, et al. 2009. Optogenetic dissection of a behavioural module in the vertebrate spinal cord. Nature 461:407-10
179. Yan QJ, RammalM, Tranfaglia M, Bauchwitz RP. 2005. Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 49:1053-66
180. YangM,BozdagiO, ScattoniML,WohrM,RoulletFI, et al. 2012. Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J. Neurosci. 32:6525-41
181. Young JJ, Cherone JM, Doyon Y, Ankoudinova I, Faraji FM, et al. 2011. Efficient targeted gene disruption in the soma and germ line of the frog Xenopus tropicalis using engineered zinc-finger nucleases. PNAS 108:7052-57
182. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, et al. 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917-20
183. Ziv L, Muto A, Schoonheim PJ, Meijsing SH, Strasser D, et al. 2013. An affective disorder in zebrafish with mutation of the glucocorticoid receptor. Mol. Psychiatry 18:681-91