Animal models offer heuristic research tools to understand the causes of human diseases and to identify potential treatments. With rapidly evolving genetic engineering technologies, mutations identified in a human disorder can be generated in the mouse genome. Phenotypic outcomes of the mutation are then explicated to confirm hypotheses about causes and to discover effective therapeutics. Most neurodevelopmental, neurodegenerative, and psychiatric disorders are diagnosed primarily by their prominent behavioral symptoms. Mouse behavioral assays analogous to the human symptoms have been developed to analyze the consequences of mutations and to evaluate proposed therapeutics preclinically. Here we describe the range of mouse behavioral tests available in the established behavioral neuroscience literature, along with examples of their translational applications. Concepts presented have been successfully used in other species, including flies, worms, fish, rats, pigs, and nonhuman primates. Identical strategies can be employed to test hypotheses about environmental causes and gene × environment interactions.


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Literature Cited

  1. Doyle A, McGarry MP, Lee NA, Lee JJ. 1.  2012. The construction of transgenic and gene knockout/knockin mouse models of human disease. Transgenic Res 21:2327–49 [Google Scholar]
  2. Aida T, Imahashi R, Tanaka K. 2.  2014. Translating human genetics into mouse: the impact of ultra-rapid in vivo genome editing. Dev. Growth Differ. 56:134–45 [Google Scholar]
  3. Buccafusco J. 3.  2000. Methods of Behavioral Analysis in Neuroscience Boca Raton, FL: CRC Press [Google Scholar]
  4. Crawley JN. 4.  1999/2007. What's Wrong With My Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice Hoboken, NJ: John Wiley & Sons, 1st and 2nd eds.. [Google Scholar]
  5. Crusio WE, Gerlai R. 5.  2013 (1999). Handbook of Molecular-Genetic Techniques for Brain and Behavior Research Amsterdam: Elsevier [Google Scholar]
  6. Gerfen C, Holmes A, Rogawski MA, Sibley DR, Skolnick P. 6.  et al. 1997–2016. Current Protocols in Neuroscience Hoboken, NJ: John Wiley & Sons [Google Scholar]
  7. Fisch GS, Flint J. 7.  2006. Transgenic and Knockout Models of Neuropsychiatric Disorders: Contemporary Clinical Neuroscience New York: Humana [Google Scholar]
  8. Pietropaolo S, Sluyter F, Crusio WE. 8.  2013. Behavioral Genetics of the Mouse 2 Genetic Mouse Models of Neurobehavioral Disorders Cambridge Handb. Behav. Genet Cambridge, UK: Cambridge Univ. Press [Google Scholar]
  9. Capecchi MR. 9.  2005. Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. Nat. Rev. Genet. 6:507–12 [Google Scholar]
  10. Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW. 10.  et al. 2013. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153:4910–18 [Google Scholar]
  11. Montoliu L, Whitelaw CB. 11.  2011. Using standard nomenclature to adequately name transgenes, knockout gene alleles and any mutation associated to a genetically modified mouse strain. Transgenic Res 20:2435–40 [Google Scholar]
  12. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F. 12.  1973. Brain dopamine and the syndromes of Parkinson and Huntington Clinical, morphological and neurochemical correlations. J. Neurol. Sci. 20:4415–55 [Google Scholar]
  13. Voikar V, Koks S, Vasar E, Rauvala H. 13.  2001. Strain and gender differences in the behavior of mouse lines commonly used in transgenic studies. Physiol. Behav. 72:271–81 [Google Scholar]
  14. Crawley JN. 14.  2008. Behavioral phenotyping strategies for mutant mice. Neuron 57:6809–18 [Google Scholar]
  15. Gold LH. 15.  1999. Hierarchical strategy for phenotypic analysis in mice. Psychopharmacology 147:2–4 [Google Scholar]
  16. Flurkey K, Currer JM, Harrison DE. 16.  2007. The mouse in aging research. The Mouse in Biomedical Research JG Fox 637–72 Burlington, MA: Elsevier [Google Scholar]
  17. Yuan R, Ackert-Bicknell C, Paigen B, Peters LL. 17.  2007. Aging study: lifespan and survival curves for 31 inbred strains of mice MPD:23401. Mouse Phenome Database, Jackson Lab., Bar Harbor, ME, retrieved Feb. 22, 2016. http://phenome.jax.org [Google Scholar]
  18. Munger S. 18.  2016. The Golden Girls of laboratory mice—Are these the oldest mice in the world?. JAX Blog Feb. 3. https://www.jax.org/news-and-insights/jax-blog/2016/february/the-golden-girls-of-laboratory-mice [Google Scholar]
  19. Crawley JN, Paylor R. 19.  1997. A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice. Horm. Behav. 31:197–211 [Google Scholar]
  20. McIlwain KL, Merriweather MY, Yuva-Paylor LA, Paylor R. 20.  2001. The use of behavioral test batteries: effects of training history. Physiol. Behav. 73:5705–17 [Google Scholar]
  21. Paylor R, Spencer CM, Yuva-Paylor LA, Pieke-Dahl S. 21.  2006. The use of behavioral test batteries, II: effect of test interval. Physiol. Behav. 87:195–102 [Google Scholar]
  22. Castrén E, Elgersma Y, Maffei L, Hagerman R. 22.  2012. Treatment of neurodevelopmental disorders in adulthood. J. Neurosci. 32:4114074–79 [Google Scholar]
  23. Happé F, Frith U. 23.  2014. Annual research review: towards a developmental neuroscience of atypical social cognition. J. Child Psychol. Psychiatry 55:6553–57 [Google Scholar]
  24. Jeste SS. 24.  2015. Neurodevelopmental behavioral and cognitive disorders. Behav. Neurol. Neuropsychiatry 21:3690–714 [Google Scholar]
  25. Johnson MH, Gliga T, Jones E, Charman T. 25.  2015. Annual research review: infant development, autism, and ADHD—early pathways to emerging disorders. J. Child Psychol. Psychiatry 56:3228–47 [Google Scholar]
  26. Rice LJ, Einfeld SL. 26.  2015. Cognitive and behavioural aspects of Prader-Willi syndrome. Curr. Opin. Psychiatry 28:2102–6 [Google Scholar]
  27. Kim YS, State MW. 27.  2014. Recent challenges to the psychiatric diagnostic nosology: a focus on the genetics and genomics of neurodevelopmental disorders. Int. J. Epidemiol. 43:2465–75 [Google Scholar]
  28. De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K. 28.  et al. 2014. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 515:7526209–15 [Google Scholar]
  29. Parikshak NN, Gandal MJ, Geschwind DH. 29.  2015. Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders. Nat. Rev. Genet. 16:8441–58 [Google Scholar]
  30. Purcell SM, Moran JL, Fromer M, Ruderfer D, Solovieff N. 30.  et al. 2014. A polygenic burden of rare disruptive mutations in schizophrenia. Nature 506:7487185–90 [Google Scholar]
  31. Bourgeron T. 31.  2015. From the genetic architecture to synaptic plasticity in autism spectrum disorder. Nat. Rev. Neurosci. 16:9551–63 [Google Scholar]
  32. Ey E, Leblond CS, Bourgeron T. 32.  2011. Behavioral profiles of mouse models for autism spectrum disorders. Autism Res 4:15–16 [Google Scholar]
  33. Kazdoba TM, Leach PT, Crawley JN. 33.  2016. Behavioral phenotypes of genetic mouse models of autism. Genes Brain Behav 15:17–26 [Google Scholar]
  34. Lord C, Bishop SL. 34.  2015. Recent advances in autism research as reflected in DSM-5 criteria for autism spectrum disorder. Annu. Rev. Clin. Psychol. 11:53–70 [Google Scholar]
  35. Wohr M, Scattoni ML. 35.  2013. Behavioural methods used in rodent models of autism spectrum disorders: current standards and new developments. Behav. Brain Res. 251:5–17 [Google Scholar]
  36. Crawley JN. 36.  2004. Designing mouse behavioral tasks relevant to autistic-like behaviors. Ment. Retard. Dev. Disabil. Res. Rev. 10:4248–58 [Google Scholar]
  37. Silverman JL, Yang M, Lord C, Crawley JN. 37.  2010. Behavioural phenotyping assays for mouse models of autism. Nat. Rev. Neurosci. 11:7490–502 [Google Scholar]
  38. Silverman JL, Crawley JN. 38.  2014. The promising trajectory of autism therapeutics discovery. Drug Discov. Today 19:7838–44 [Google Scholar]
  39. Nadler JJ, Moy SS, Dold G, Trang D, Simmons N. 39.  et al. 2004. Automated apparatus for quantitation of social approach behaviors in mice. Genes Brain Behav 3:5303–14 [Google Scholar]
  40. Yang M, Silverman JL, Crawley JN. 40.  2011. Automated three-chambered social approach task for mice. Curr. Protoc. Neurosci. 8:8.26.1–16 [Google Scholar]
  41. Bolivar VJ, Walters SR, Phoenix JL. 41.  2007. Assessing autism-like behavior in mice: variations in social interactions among inbred strains. Behav. Brain Res. 176:121–26 [Google Scholar]
  42. Brodken ES. 42.  2007. BALB/c mice: low sociability and other phenotypes that may be relevant to autism. Behav. Brain Res. 176:153–65 [Google Scholar]
  43. Moy SS, Nadler JJ, Young NB, Perez A, Holloway LP. 43.  et al. 2007. Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains. Behav. Brain Res. 176:14–20 [Google Scholar]
  44. McFarlane HG, Kusek GK, Yang M, Phoenix JL, Bolivar VJ, Crawley JN. 44.  2008. Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes Brain Behav 7:2152–63 [Google Scholar]
  45. DeLorey TM, Sahbaie P, Hashemi E, Homanics GE, Clark JD. 45.  2008. Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: a potential model of autism spectrum disorder. Behav. Brain Res. 187:2207–20 [Google Scholar]
  46. Page DT, Kuti OJ, Prestia C, Sur M. 46.  2009. Haploinsufficiency for Pten and Serotonin transporter cooperatively influences brain size and social behavior. PNAS 106:61989–94 [Google Scholar]
  47. Peñagarikano O, Lázaro MT, Lu X-H, Gordon A, Dong H. 47.  et al. 2015. Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism. Sci. Transl. Med. 7:271271ra8 [Google Scholar]
  48. Lázaro MT, Golshani P. 48.  2015. The utility of rodent models of autism spectrum disorders. Curr. Opin. Neurol. 28:2103–9 [Google Scholar]
  49. Burket JA, Benson AD, Tang AH, Deutsch SI. 49.  2013. D-Cycloserine improves sociability in the BTBR T + Itpr3tf/J mouse model of autism spectrum disorders with altered Ras/Raf/ERK1/2 signaling. Brain Res. Bull. 96:62–70 [Google Scholar]
  50. Panksepp JB, Lahvis GP. 50.  2016. Differential influence of social versus isolate housing on vicarious fear learning in adolescent mice. Behav. Neurosci. 130:2206–11 [Google Scholar]
  51. Tsai PT, Hull C, Chu Y, Greene-Colozzi E, Sadowski AR. 51.  et al. 2012. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature 488:7413647–51 [Google Scholar]
  52. Schmeisser MJ, Ey E, Wegener S, Bockmann J, Stempel AV. 52.  et al. 2012. Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature 486:7402256–60 [Google Scholar]
  53. Silverman JL, Pride MC, Hayes JE, Puhger KR, Butler-Struben HM. 53.  et al. 2015. GABAB receptor agonist R-baclofen reverses social deficits and reduces repetitive behavior in two mouse models of autism. Neuropsychopharmacology 40:92228–39 [Google Scholar]
  54. Mei Y, Monteiro P, Zhou Y, Kim JA, Gao X. 54.  et al. 2016. Adult restoration of Shank3 expression rescues selective autistic-like phenotypes. Nature 530:7591481–84 [Google Scholar]
  55. Cope ZA, Powell SB, Young JW. 55.  2016. Modeling neurodevelopmental cognitive deficits in tasks with cross-species translational validity. Genes Brain Behav 15:127–44 [Google Scholar]
  56. Vaquer G, Rivière F, Mavris M, Bignami F, Llinares-Garcia J. 56.  et al. 2013. Animal models for metabolic, neuromuscular and ophthalmological rare diseases. Nat. Rev. Drug Discov. 12:4287–305 [Google Scholar]
  57. Onos KD, Sukoff Rizzo SJ, Howell GR, Sasner M. 57.  2015. Toward more predictive genetic mouse models of Alzheimer's disease. Brain Res. Bull. 122:1–11 [Google Scholar]
  58. Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E. 58.  2011. Alzheimer's disease. Lancet 377:1019–31 [Google Scholar]
  59. Puzzo D, Lee L, Palmeri A, Calabrese G, Arancio O. 59.  2014. Behavioral assays with mouse models of Alzheimer's disease: practical considerations and guidelines. Biochem. Pharmacol. 88:450–67 [Google Scholar]
  60. Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ. 60.  2014. Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front. Genet. 5:88 [Google Scholar]
  61. Rodgers SP, Born HA, Das P, Jankowsky JL. 61.  2012. Transgenic APP expression during postnatal development causes persistent locomotor hyperactivity in the adult. Mol. Neurodegener. 7:28 [Google Scholar]
  62. Stella F, Laks J, Govone JS, de Medeiros K, Forlenza OV. 62.  2015. Association of neuropsychiatric syndromes with global clinical deterioration in Alzheimer's disease patients. Int. Psychogeriatr. 17:1–8 [Google Scholar]
  63. Levenson RW, Sturm VE, Haase CM. 63.  2014. Emotional and behavioral symptoms in neurodegenerative disease: a model for studying the neural bases of psychopathology. Annu. Rev. Clin. Psychol. 10:581–606 [Google Scholar]
  64. Jankovic J. 64.  2008. Parkinson's disease: clinical features and diagnosis. J. Neurol. Neurosurg. Psychiatry 79:4368–76 [Google Scholar]
  65. Shulman LM, Taback RL, Bean J, Weiner WJ. 65.  2001. Comorbidity of the nonmotor symptoms of Parkinson's disease. Mov. Disord. 16:507–10 [Google Scholar]
  66. Chaudhuri KR, Healy DG, Schapira AH. 66.  2006. Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol 5:235–45 [Google Scholar]
  67. Ziemssen T, Reichmann H. 67.  2007. Non-motor dysfunction in Parkinson's disease. Parkinsonism Relat. Disord. 13:323–32 [Google Scholar]
  68. Postuma RB, Aarsland D, Barone P, Burn DJ, Hawkes CH. 68.  et al. 2012. Identifying prodromal Parkinson's disease: pre-motor disorders in Parkinson's disease. Mov. Disord. 27:5617–26 [Google Scholar]
  69. Kalia LV, Lang AE. 69.  2015. Parkinson's disease. Lancet 386:9996896–912 [Google Scholar]
  70. Taylor TN, Greene JG, Miller GW. 70.  2010. Behavioral phenotyping of mouse models of Parkinson's disease. Behav. Brain Res. 211:11–10 [Google Scholar]
  71. Smith GA, Isacson O, Dunnett SB. 71.  2012. The search for genetic mouse models of prodromal Parkinson's disease. Exp. Neurol. 237:2267–73 [Google Scholar]
  72. Li X, Redus L, Chen C, Martinez PA, Strong R. 72.  et al. 2013. Cognitive dysfunction precedes the onset of motor symptoms in the MitoPark mouse model of Parkinson's disease. PLOS ONE 8:8e71341 [Google Scholar]
  73. 73. Huntingt. Dis. Collab. Res. Group 1993. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72:6971–83 [Google Scholar]
  74. Langbehn DR, Hayden MR, Paulsen JS. 74.  PREDICT-HD Investig. Huntingt. Study Group 2010. CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approaches. Am. J. Med. Genet. B Neuropsychiatr. Genet. 153B:2397–408 [Google Scholar]
  75. Menalled L, El-Khodor BF, Patry M, Suárez-Fariñas M, Orenstein SJ. 75.  et al. 2009. Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models. Neurobiol. Dis. 35:3319–36 [Google Scholar]
  76. Yang WX, Gray M. 76.  2011. Mouse models for validating preclinical candidates for Huntington's disease. Neurobiology of Huntington's Disease: Applications to Drug Discovery DC Lo, RE Hughes Boca Raton, FL: CRC Press/Taylor & Francis [Google Scholar]
  77. Lee CY, Cantle JP, Yang XW. 77.  2013. Genetic manipulations of mutant huntingtin in mice: new insights into Huntington's disease pathogenesis. FEBS J 280:184382–94 [Google Scholar]
  78. Ray DE, Ira S. 78.  2011. Huntington's disease clinical experimental therapeutics. Neurobiology of Huntington's Disease: Applications to Drug Discovery DC Lo, RE Hughes Boca Raton, FL: CRC Press/Taylor & Francis [Google Scholar]
  79. Binder EB. 79.  2012. The genetic basis of mood and anxiety disorders—changing paradigms. Biol. Mood Anxiety Disord. 2:17 [Google Scholar]
  80. 80. Schizophr. Work. Group Psychiatr. Genom. Consort 2014. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511:7510421–27 [Google Scholar]
  81. 81. Am. Psychiatr. Assoc 1994. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC:: Am. Psychiatr. Assoc, 4th ed.. [Google Scholar]
  82. Cryan JF, Holmes A. 82.  2005. The ascent of mouse: advances in modelling human depression and anxiety. Nat. Rev. Drug Discov. 4:9775–90 [Google Scholar]
  83. Andreasen NC. 83.  1995. Symptoms, signs, and diagnosis of schizophrenia. Lancet 346:477–81 [Google Scholar]
  84. Powell CM, Miyakawa T. 84.  2006. Schizophrenia-relevant behavioral testing in rodent models: A uniquely human disorder?. Biol. Psychiatry 59:121198–207 [Google Scholar]
  85. Javitt DC, Zukin SR. 85.  1991. Recent advances in the phencyclidine model of schizophrenia. Am. J. Psychiatry 148:1301–8 [Google Scholar]
  86. Luby ED, Cohen BD, Rosenbaum G, Gottlieb JS, Kelly R. 86.  1959. Study of a new schizophrenic-like drug—Sernyl. Arch. Neurol. Psychiatry 81:363–69 [Google Scholar]
  87. Ital T, Keskiner A, Kiremitci N, Holden JMC. 87.  1967. Effect of phencyclidine in chronic schizophrenics. Can. Psychiatr. Assoc. J. 12:209–12 [Google Scholar]
  88. Jones C, Watson D, Fone K. 88.  2011. Animal models of schizophrenia. Br. J. Pharmacol. 164:41162–94 [Google Scholar]
  89. Geyer MA. 89.  2008. Developing translational animal models for symptoms of schizophrenia or bipolar mania. Neurotox. Res. 14:171–78 [Google Scholar]
  90. Mar AC, Horner AE, Nilsson SR, Alsiö J, Kent BA. 90.  et al. 2013. The touchscreen operant platform for assessing executive function in rats and mice. Nat. Protoc. 8:101985–2005 [Google Scholar]
  91. Sokolowska E, Hovatta I. 91.  2013. Anxiety genetics—findings from cross-species genome-wide approaches. Biol. Mood Anxiety Disord. 3:9 [Google Scholar]
  92. Steimer T. 92.  2011. Animal models of anxiety disorders in rats and mice: some conceptual issues. Dialogues Clin. Neurosci. 13:4495–506 [Google Scholar]
  93. Griebel G, Holmes A. 93.  2013. 50 years of hurdles and hope in anxiolytic drug discovery. Nat. Rev. Drug Discov. 12:9667–87 [Google Scholar]
  94. Yang H, Bell TA, Churchill GA, Pardo-Manuel de Villena. 94.  2007. On the subspecific origin of the laboratory mouse. Nat. Genet. 39:91100–7 [Google Scholar]
  95. Chesler EJ. 95.  2014. Out of the bottleneck: the Diversity Outcross and Collaborative Cross mouse populations in behavioral genetics research. Mamm. Genome 25:3–11 [Google Scholar]
  96. Churchill GA, Airey DC, Allayee H, Angel JM, Attie AD. 96.  et al. 2004. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat. Genet. 36:111133–37 [Google Scholar]
  97. Brown SA. 97.  2015. Building SuperModels: emerging patient avatars for use in precision and systems medicine. Front. Physiol. 6:318 [Google Scholar]
  98. Malaney P, Nicosia SV, Davé V. 98.  2014. One mouse, one patient paradigm: new avatars of personalized cancer therapy. Cancer Lett 344:11–12 [Google Scholar]
  99. Marchetto MC, Brennand KJ, Boyer LF, Gage FH. 99.  2011. Induced pluripotent stem cells (iPSCs) and neurological disease modeling: progress and promises. Hum. Mol. Genet. 20:R2R109–15 [Google Scholar]
  100. Santostefano KE, Hamazaki T, Biel NM, Jin S, Umezawa A, Terada N. 100.  2015. A practical guide to induced pluripotent stem cell research using patient samples. Lab. Investig. 95:14–13 [Google Scholar]
  101. Russo FB, Cugola FR, Fernandes IR, Pignatari GC, Beltrão-Braga PCB. 101.  2015. Induced pluripotent stem cells for modeling neurological disorders. World J. Transpl. 5:4209–21 [Google Scholar]
  102. Brielmaier J, Matteson PG, Silverman JL, Senerth JM, Kelly S. 102.  et al. 2012. Autism-relevant social abnormalities and cognitive deficits in engrailed-2 knockout mice. PLOS ONE 7:7e40914 [Google Scholar]
  103. Peca J, Feliciano C, Ting JT, Wang W, Wells MF. 103.  et al. 2011. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472:7344437–42 [Google Scholar]
  104. Ju A, Hammerschmidt K, Tantra M, Krueger D, Brose N, Ehrenreich H. 104.  2014. Juvenile manifestation of ultrasound communication deficits in the neuroligin-4 null mutant mouse model of autism. Behav. Brain Res. 270:159–64 [Google Scholar]
  105. Horev G, Ellegood J, Lerch JP, Son YE, Muthuswamy L. 105.  et al. 2011. Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism. PNAS 108:4117076–81 [Google Scholar]
  106. MacQueen GM, Ramakrishnan K, Croll SD, Siuciak JA, Yu G. 106.  et al. 2001. Performance of heterozygous brain-derived neurotrophic factor knockout mice on behavioral analogues of anxiety, nociception, and depression. Behav. Neurosci. 115:51145–53 [Google Scholar]
  107. Yu H, Wang DD, Wang Y, Liu T, Lee FS, Chen ZY. 107.  2012. Variant brain-derived neurotrophic factor Val66Met polymorphism alters vulnerability to stress and response to antidepressants. J. Neurosci. 32:124092–101 [Google Scholar]
  108. Xiang J, Yan S, Li SH, Li XJ. 108.  2015. Postnatal loss of Hap1 reduces hippocampal neurogenesis and causes adult depressive-like behavior in mice. PLOS Genet 11:4e1005175 [Google Scholar]
  109. Bartolomucci A, Carola V, Pascucci T, Puglisi-Allegra S, Cabib S. 109.  et al. 2010. Increased vulnerability to psychosocial stress in heterozygous serotonin transporter knockout mice. Dis. Model. Mech. 3:7–8459–70 [Google Scholar]
  110. Sanders AC, Hussain AJ, Hen R, Zhuang X. 110.  2007. Chronic blockade or constitutive deletion of the serotonin transporter reduces operant responding for food reward. Neuropsychopharmacology 32:112321–29 [Google Scholar]
  111. Allen GC, Qu X, Earnest DJ. 111.  2005. TrkB-deficient mice show diminished phase shifts of the circadian activity rhythm in response to light. Neurosci. Lett. 378:3150–55 [Google Scholar]
  112. Linnarsson S, Björklund A, Ernfors P. 112.  1997. Learning deficit in BDNF mutant mice. Eur. J. Neurosci. 9:122581–87 [Google Scholar]
  113. Ramboz S, Oosting R, Amara DA, Kung HF, Blier P. 113.  et al. 1998. Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. PNAS 95:14476–81 [Google Scholar]
  114. Heisler LK, Chu HM, Brennan TJ, Danao JA, Bajwa P. 114.  et al. 1988. Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice. PNAS 95:15049–54 [Google Scholar]
  115. Lifschytz T, Broner EC, Zozulinsky P, Slonimsky A, Eitan R. 115.  et al. 2012. Relationship between Rgs2 gene expression level and anxiety and depression-like behaviour in a mutant mouse model: serotonergic involvement. Int. J. Neuropsychopharmacol. 15:91307–18 [Google Scholar]
  116. Oliveira-dos-Santos AJ, Matsumoto G, Snow BE. 116.  et al. 2000. Regulation of T cell activation, anxiety, and male aggression by RGS2. PNAS 97:2212272–77 [Google Scholar]
  117. Bodnoff SR, Suranyi-Cadotte B, Quirion R, Meaney MJ. 117.  1989. A comparison of the effects of diazepam versus several typical and atypical anti-depressant drugs in an animal model of anxiety. Psychopharmacology 97:277–79 [Google Scholar]
  118. Gross C, Santarelli L, Brunner D, Zhuang X, Hen R. 118.  2000. Altered fear circuits in 5-HT1A receptor KO mice. Biol. Psychiatry 48:121157–63 [Google Scholar]
  119. Pattij T, Groenink L, Hijzen TH, Oosting RS, Maes RA. 119.  et al. 2002. Autonomic changes associated with enhanced anxiety in 5-HT1A receptor knockout mice. Neuropsychopharmacology 27:3380–90 [Google Scholar]
  120. Johnson AW, Jaaro-Peled H, Shahani N, Sedlak TW, Zoubovsky S. 120.  et al. 2013. Cognitive and motivational deficits together with prefrontal oxidative stress in a mouse model for neuropsychiatric illness. PNAS 110:3012462–67 [Google Scholar]
  121. Finlay JM, Dunham GA, Isherwood AM, Newton CJ, Nguyen TV. 121.  et al. 2015. Effects of prefrontal cortex and hippocampal NMDA-NR1 subunit deletion on complex cognitive and social behaviors. Brain Res 1600:70–83 [Google Scholar]
  122. Clapcote SJ, Lipina TV, Millar JK, Mackie S, Christie S. 122.  et al. 2007. Behavioral phenotypes of Disc1 missense mutations in mice. Neuron 54:3387–402 [Google Scholar]
  123. Papaleo F, Yang F, Garcia S, Chen J, Lu B. 123.  et al. 2012. Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like behaviors via dopamine/D2 pathways. Mol. Psychiatry 17:185–98 [Google Scholar]
  124. Vuillermot S, Joodmardi E, Perlmann T, Ove Ögren S, Feldon J, Meyer U. 124.  2011. Schizophrenia-relevant behaviors in a genetic mouse model of constitutive Nurr1 deficiency. Genes Brain Behav 10:589–603 [Google Scholar]
  125. Young JW, Kamenski ME, Higa KK, Light GA, Geyer MA, Zhou X. 125.  2015. GlyT-1 inhibition attenuates attentional but not learning or motivational deficits of the Sp4 hypomorphic mouse model relevant to psychiatric disorders. Neuropsychopharmacology 40:122715–26 [Google Scholar]
  126. Gómez-Sintes R, Kvajo M, Gogos JA, Lucas JJ. 126.  2014. Mice with a naturally occurring DISC1 mutation display a broad spectrum of behaviors associated to psychiatric disorders. Front. Behav. Neurosci. 8:253 [Google Scholar]
  127. Dodart JC, Meziane H, Mathis C, Bales KR, Paul SM, Ungerer A. 127.  1999. Behavioral disturbances in transgenic mice overexpressing the V717F β-amyloid precursor protein. Behav. Neurosci. 113:982–90 [Google Scholar]
  128. Nilsson LN, Arendash GW, Leighty RE, Costa DA, Low MA. 128.  et al. 2004. Cognitive impairment in PDAPP mice depends on ApoE and ACT-catalyzed amyloid formation. Neurobiol. Aging 25:1153–67 [Google Scholar]
  129. Ohno M, Chang L, Tseng W, Oakley H, Citron M. 129.  et al. 2006. Temporal memory deficits in Alzheimer's mouse models: rescue by genetic deletion of BACE1. Eur. J. Neurosci. 23:251–60 [Google Scholar]
  130. Davis KE, Easton A, Eacott MJ, Gigg J. 130.  2013. Episodic-like memory for what-where-which occasion is selectively impaired in the 3xTgAD mouse model of Alzheimer's disease. J. Alzheimers Dis. 33:3681–98 [Google Scholar]
  131. Shukla V, Zheng YL, Mishra SK, Amin ND, Steiner J. 131.  et al. 2013. A truncated peptide from p35, a Cdk5 activator, prevents Alzheimer's disease phenotypes in model mice. FASEB J 27:1174–86 [Google Scholar]
  132. Devi L, Ohno M. 132.  2012. 7,8-Dihydroxyflavone, a small-molecule TrkB agonist, reverses memory deficits and BACE1 elevation in a mouse model of Alzheimer's disease. Neuropsychopharmacology 37:2434–44 [Google Scholar]
  133. Tesseur I, Van Dorpe J, Bruynseels K, Bronfman F, Sciot R. 133.  et al. 2000. Prominent axonopathy and disruption of axonal transport in transgenic mice expressing human apolipoprotein E4 in neurons of brain and spinal cord. Am. J. Pathol. 157:1495–510 [Google Scholar]
  134. Lazarov O, Morfini GA, Pigino G, Gadadhar A, Chen X. 134.  et al. 2007. Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer's disease-linked mutant presenilin 1. J. Neurosci. 27:267011–20 [Google Scholar]
  135. Alexander G, Hanna A, Serna V, Younkin L, Younkin S, Janus C. 135.  2011. Increased aggression in males in transgenic Tg2576 mouse model of Alzheimer's disease. Behav. Brain Res. 216:177–83 [Google Scholar]
  136. Wisor JP, Edgar DM, Yesavage J, Ryan HS, McCormick CM. 136.  et al. 2005. Sleep and circadian abnormalities in a transgenic mouse model of Alzheimer's disease: a role for cholinergic transmission. Neuroscience 131:2375–85 [Google Scholar]
  137. Carter RJ, Morton J, Dunnett SB. 137.  2012. Motor coordination and balance in rodents. Curr. Protoc. Neurosci. 8:8.12.1–14 [Google Scholar]
  138. Paumier KL, Sukoff Rizzo SJ, Berger Z, Chen Y, Gonzales C. 138.  et al. 2013. Behavioral characterization of A53T mice reveals early and late stage deficits related to Parkinson's disease. PLOS ONE 8:8e70274 [Google Scholar]
  139. Fleming SM, Salcedo J, Fernagut PO, Rockenstein E, Masliah E. 139.  et al. 2004. Early and progressive sensorimotor anomalies in mice overexpressing wild-type human α-synuclein. J. Neurosci. 24:429434–40 [Google Scholar]
  140. Magen I, Fleming SM, Zhu C, Garcia EC, Cardiff KM. 140.  et al. 2012. Cognitive deficits in a mouse model of pre-manifest Parkinson's disease. Eur. J. Neurosci. 35:6870–82 [Google Scholar]
  141. Farrell KF, Krishnamachari S, Villanueva E, Lou H, Alerte TN. 141.  et al. 2014. Non-motor parkinsonian pathology in aging A53T α-synuclein mice is associated with progressive synucleinopathy and altered enzymatic function. J. Neurochem. 128:4536–46 [Google Scholar]
  142. Bichler Z, Lim HC, Zeng L, Tan EK. 142.  2013. Non-motor and motor features in LRRK2 transgenic mice. PLOS ONE 8:7e70249 [Google Scholar]
  143. Wang L, Fleming SM, Chesselet MF, Taché Y. 143.  2008. Abnormal colonic motility in mice overexpressing human wild-type α-synuclein. Neuroreport 19:8873–76 [Google Scholar]
  144. Fleming SM, Tetreault NA, Mulligan CK, Hutson CB, Masliah E, Chesselet MF. 144.  2008. Olfactory deficits in mice overexpressing human wildtype α-synuclein. Eur. J. Neurosci. 28:247–56 [Google Scholar]
  145. Hickey MA, Gallant K, Gross GG, Levine MS, Chesselet MF. 145.  2005. Early behavioral deficits in R6/2 mice suitable for use in preclinical drug testing. Neurobiol. Dis. 20:11–11 [Google Scholar]
  146. Menalled LB, Kudwa AE, Miller S, Fitzpatrick J, Watson-Johnson J. 146.  et al. 2012. Comprehensive behavioral and molecular characterization of a new knock-in mouse model of Huntington's disease: zQ175. PLOS ONE 7:12e49838 [Google Scholar]

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