RUMPSHAKER - AN X-LINKED MUTATION AFFECTING CNS MYELINATION - A STUDY OF THE FEMALE HETEROZYGOTE

This study examines the myelin deficits found in the spinal cord and optic nerves of female mice heterozygotes for rumpshaker (rsh), an X-linked mutation causing hypomyelination. No clinical abnormalities were detected but morphological changes were evident, particularly in the spinal cord, which showed no evidence of resolving with age. In the spinal cord, scattered hypomyelinated axons, occasionally grouped in twos or threes, were the major feature; oligodendrocyte numbers were slightly elevated at all ages compared to normal male littermates and the total amount of myelin was reduced. Myelin protein composition of the sheaths was examined by immunostaining for myelin basic protein (MBP) and two peptide regions of PLP/DM-20 molecule; one being proteolipid protein (PLP)-specific and the other recognizing the c-terminal common to PLP-DM-20. The majority of myelin sheaths immunostained for MBP and PLP. Occasional MBP-positive sheaths failed to stain with PLP/DM-20 or PLP-specific antiserum. Therefore, at least two types of immunocytochemically-defined myelin sheaths are present in the heterozygotes. Changes in the optic nerves were much less obvious; glial cell numbers were increased but thinly myelinated axons were not detected although the total amount of myelin was reduced compared to normal littermates. In no instance were mosaic, amyelinated/hypomyelinated patches detected. Heterozygotes for rsh, therefore, are considerably different from those for other X-linked myelin mutations like the jimpy mouse and the myelin-deficient rat, both in regard to the severity of the lesions and their failure to recover with age.