Motor function analysis of myelin mutant mice using a rotarod

Abstract

We have examined motor control in normal and shiverer mutant mice using the rotarod assay, a forced motor activity which tests for balance and co-ordination. Shiverer mice carry a deletion of the myelin basic protein (MBP) gene, resulting in CNS dysmyelination and characteristics motor dysfunction. Homozygous mutant mice had a significant increase in cumulative falls from the rotatod relative to heterozygous mice. Non-acclimated animals of both genotypes showed progressive improvement in performance when tested on successive days. The rotarod test also discriminited shiverer mutants from animals that received gene therapy intervention. Shiverer animals carrying an MBP transgene showed gene-dosage-dependent improvements in motor function, and mutants which received thalamic transplants of wild type oligodendrocyte precursor cells showed improvement relative to sham operated and non-transplanted controls. Thus the rotarod is a sensitive measure of motor function in hypomyelinated mice, and may be useful for assessing the results of experimental manipulations including transgenic gene therapy and cell transplantation.