Abstract
Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However, 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. Lastly, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.
Highlights
Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders
We identified genetic loci associated with motor performance and body weight using Collaborative Cross (CC)
Our results show that rotarod performance and body weight are highly variable among different strains of the CC, demonstrating that the Collaborative Cross provides an excellent platform for studying interactions between body weight, neurological disease and genotype
Summary
Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. We used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. 45 loci affected rotarod performance, seven of which were associated with body weight, suggesting a strong link at the genetic level. Impaired motor function is associated with a broad spectrum of human conditions including neurodegenerative diseases, and neurological and neurodevelopmental disorders. Loci and genes associated with numerous diseases and phenotypic traits, including body weight, obesity and neurological disorders[6,7,8,9]. This resource, which was established by combining the genomes of eight diverse founder strains
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