Влияние точечных мутаций в гене Disc1 у мышей линий L100P и Q31L на формирование поведения, подобного обсессивно-компульсивному

Abstract

Obsessive-compulsive disorder (OCD) is a widespread mental disorder, which leads to social disability of the patient. OCD is a key example of a number of conditions known as obsessive-compulsive and related disorders. These disorders are clinically heterogeneous and etiologically complex and their main pathophysiological mechanisms are still unknown. An important role in understanding the pathogenesis of OCD is played by models of this disease obtained in laboratory animals that provide an understanding of the molecular basis of stereotyped behavior and the genetic architecture of OCD. One of the OCD genetic models is the mice with a deletion of exons 2 and 3 of the Disc1 gene (disrupted in schizophrenia 1). Mutations in the Disc1 gene are associated with the development of schizophrenia in humans, which is known to be associated with obsessive-compulsive behavior. In this work, we used two mouse strains with point mutations in the Disc1 gene (L100P and Q31L strains) to isolate the locus of this gene responsible for the formation of OCD-like behavior. We have shown that Q31L amino acid substitution leads to the development of behavioral phenotype associated with repetitive actions in the marble burying test, while the L100P substitution does not lead to the formation of such phenotype. In addition, we showed that the OCD-like behavior is caused by the deficiency of the serotonergic system, since an intraperitoneal injection of the metabolic precursor of serotonin - 5-hydroxytryptophan (5-HTP) rescued the behavioral phenotype observed in the marble burying test.