Behavior phenotyping of heterozygous mice with mutations L100P and Q31L in the DISC1 gene

N.D. Chizhova1, MS student,
T.V. Lipina2, Doctor of biological sciences, Head of the laboratory of experimental models of the pathology of cognition and emotions, Chief Scientist,
T.G. Amstislavskaya1, 2, Doctor of biological sciences, Head of the laboratory of translational biopsychiatry, Deputy Director for Science, Chief Scientist

1Novosibirsk State University

Russia, 630090, Pirogova Str. 2, Novosibirsk

2Federal State Budgetary Scientific Institution «Scientific Research Institute of Physiology and Basic Medicine»

Russia, 630117, Timakova Str. 4, Novosibirsk

Е-mail: chnadezhda1995@gmail.com

Abstract

Schizophrenia and depression are multifactor diseases, which pathogenesis include a complex interaction of the genetic characteristics of the organism and environmental factors. These diseases often overlap with each other, both in a number of negative symptoms and in relation to factors that increase the risk of development, which, in turn, implies a potential coincidence in the pathophysiology and/or etiology of these disorders. Based on numerous studies, genetic associations have been established between the DISC1 (Disrupted-In-Schizophrenia-1) gene locus and psychiatric diseases in divers human populations. In particular, it was shown that biological processes in neurons resulting from the participation of the protein DISC1 and its interactome can affect the development of schizophrenia and depression. Valid animal DISC1 genetic models of psychopathology data have been developed to study these biochemical processes and test new therapies. So, as a part of the unique scientific installation “Biological collection – genetic biomodels of neuropsychiatric diseases” (Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk), there are mice of two genetic lines (DISC1-L100P–/– and DISC1-Q31L–/–), which demonstrate endophenotypes of schizophrenia and depression, respectively. In the present study mice with combination of different mutant alleles of the DISC1 gene (L100P and Q31L) have been obtained and phenotypic features of their emotional, social and cognitive behavior have been investigated. It was elicited differences and similarities in DISC1-L100P/Q31L mice compared with L100P+/– in some tests and with Q31L+/– in others. The revealed gender differences in the expression of individual behavioral patterns, as well as the presence of cognitive impairment in the PPI test, allow us to consider mice DISC1-L100P+/–/Q31L+/– as a promising experimental model of schizophrenia.

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