Genetic mouse models of schizophrenia: from hypothesis-based to susceptibility gene-based models.
Translation of human genetic mutations into genetic mouse models is an important strategy to study the pathogenesis of schizophrenia, identify potential drug targets, and test new drugs for new antipsychotic treatments. Although it is impossible to recapitulate the full spectrum of schizophrenia symptoms in animal models, hypothesis-driven genetic mouse models have been successful in reproducing several schizophrenia-like behaviors and uncovering the roles of specific genes in dopamine and glutamine neurotransmission systems in mediating schizophrenia-like behaviors. Recent discoveries of susceptibility genes for schizophrenia and recognition of cognitive dysfunction as a core feature of schizophrenia and a phenotype of susceptibility for schizophrenia offer opportunities to develop newer genetic mouse models based on susceptibility. This new generation of genetic mouse models could shed light on the etiology of schizophrenia and lead us to new hypotheses, novel diagnostic tools, and more effective therapy.
Chen
Jingshan
J
Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. jingshan.chen@mail.nih.gov
Lipska
Barbara K
BK
Weinberger
Daniel R
DR
D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004298:Dopamine / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics* / Q000523:psychology; D005973:Glutamine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D012559:Schizophrenia / Q000235:genetics*
D005973:Glutamine; D004298:Dopamine