Behavioral abnormalities in a genetic model of Duchenne myodystrophy in mice

Mutations in the Dmd gene encoding the membrane protein dystrophin are associated with the development of severe X-linked muscle diseases Duchenne and Becker myodystrophy. At the same time, along with the classic symptoms of striated muscles, dystrophin mutations can lead to a decrease in cognitive functions and behavioral abnormalities. Objective: conducting a pilot analysis of behavioral and cognitive characteristics in mice with a genetic defect that reproduces the phenotype of Duchenne myodystrophy. Materials and methods. To assess the features of motor functions and behavior, DmdDel8-34(n=13) and control animals of the wild type (n=12) were subjected to research in the tests "Load retention", "Rotarod", "Elevated plus maze" and "Object recognition". Results. It was found that mice carrying the DmdDel8-34 mutation are characterized by a decrease in motor functions, show signs of anxiety, and also show low exploratory activity. The detected features of the cognitive and emotional status are consistent with clinical observations indicating an increased risk of developing autism spectrum disorders and obsessive-compulsive disorder in patients with Dmd gene mutations. Thus, it was proved that from the 8th week of life, mice of the DmdDel8-34 line show a decrease in performance in the Rotarod and Load Retention tests. Behavioral testing in the Elevated Plus Maze test revealed a decrease in time reaching a statistically significant difference compared to the wild-type control at week 12, and when assessing cognitive functions in the Object Recognition test, it was shown that DmdDel8-34mice show an increase in the discrimination index value, which is a sign of increased efficiency of hippocampal memory. Conclusion. The study made it possible to identify some behavioral anomalies in genetically modified mice carrying a large deletion of exons 8-34 of the Dmd gene encoding dystrophin.