Investigating Motor Coordination Using BXD Recombinant Inbred Mice to Model the Genetic Underpinnings of Developmental Coordination Disorder

Abstract

The fundamental skills for motor coordination and motor control emerge through development. Neurodevelopmental disorders such as developmental coordination disorder (DCD) lead to impaired acquisition of motor skills. This study investigated motor behaviors that reflect the core symptoms of human DCD through the use of BXD recombinant inbred strains of mice that are known to have divergent phenotypes in many behavioral traits, including motor activity. We sought to correlate behavior in basic motor control tasks with the known genotypes of these reference populations of mice using quantitative trait locus (QTL) mapping. We used 12 BXD strains with an average of 16 mice per group to assess the onset of reflexes during the early neonatal stage of life and differences in motor coordination using the tests for open field, rotarod, and gait behaviors during the adolescent/young adulthood period. Results indicated significant variability between strains in when neonatal reflexes appeared and significant strain differences for all measures of motor coordination. Five strains (BXD15, BXD27, BXD28, BXD75, BXD86) struggled with sensorimotor coordination as seen in gait analysis, rotarod, and open field, similar to human presentation of DCD. We identified three significant quantitative trait loci for gait on proximal Chr 3, Chr 4, and distal Chr 6. Based on expression, function, and polymorphism within the mapped QTL intervals, seven candidate genes (Gpr63, Spata5, Trpc3, Cntn6, Chl1, Grm7, Ogg1) emerged. This study offers new insights into mouse motor behavior, which promises to be a first murine model to explore the genetics and neural correlates of DCD.