MOTOR FUNCTION-ANALYSIS OF MYELIN MUTANT MICE USING A ROTAROD

We have examined motor control in normal and shiverer mutant mice usin g the rotarod assay, a forced motor activity which tests for balance a nd co-ordination. Shiverer mice carry a deletion of the myelin basic p rotein (MBP) gene, resulting in CNS dysmyelination and characteristic motor dysfunction. Homozygous mutant mice had a significant increase i n cumulative falls from the rotarod relative to heterozygous mice. Non -acclimated animals of both genotypes showed progressive improvement i n performance when tested on successive days. The rotarod test also di scriminated shiverer mutants from animals that received gene therapy i ntervention. Shiverer animals carrying an MBP transgene showed gene-do sage-dependent improvements in motor function, and mutants which recei ved thalamic transplants of wild type oligodendrocyte precursor cells showed improvement relative to sham operated and non-transplanted cont rols. Thus the rotarod is a sensitive measure of motor function in hyp omyelinated mice, and may be useful for assessing the results of exper imental manipulations including transgenic gene therapy and cell trans plantation.