G.P.31: Voluntary running wheel activity and body weight analyses in diverse mouse strains: A platform for identifying modifying genes for neuromuscular diseases

Abstract

Analysis of voluntary running wheel activity in mice is a useful phenotypic measure of skeletal muscle function. We have collected voluntary running wheel activity and total body weight data from >50 strains of mice belonging to the ‘Collaborative Cross' (aka The Gene Mine), and compared these to known models of neuromuscular disease. The Gene Mine is a mouse reference population derived from eight genetically diverse founder strains, with the genome of each offspring strain being a mosaic of chromosomal segments inherited randomly from the founders. The Gene Mine is designed specifically for complex trait analysis and the identification of quantitative trait loci (QTL). Our analyses of voluntary running wheel activity has involved measuring distance, maximum speed, average speed and time spent on the wheel over a six day consecutive period in male and female Gene Mine mice at two different ages (6weeks and 6–9months). We also recorded real-time activity levels and are imaging selected mouse strains by magnetic resonance imaging and computed tomography. Our results indicate marked phenotypic variation across all traits measured, including comparisons of young and older Gene Mine mice. We are now mapping QTL for the various phenotypes and comparing these with skeletal muscle gene expression. We previously crossed skeletal muscle actin knockout mice with Gene Mine strains to identify strains capable of extending the usual early lethal phenotype of this model. The phenotype resource we and others are building can now be used to search for strains, and from there QTL, that modify voluntary running wheel activity, weight and muscle bulk in various models of neuromuscular diseases.