CHROMOSOMAL LOCALIZATION OF THE MYELIN-ASSOCIATED OLIGODENDROCYTIC BASIC-PROTEIN AND EXPRESSION IN THE GENETICALLY LINKED NEUROLOGICAL MOUSE MUTANTS DUCKY AND TIPPY

The alternatively spliced cDNAs encoding the myelin-associated/oligode ndrocytic basic proteins (MOBPs) have recently been identified in rat. The Mobp gene maps to the distal part of mouse chromosome 9 at a regi on syntenic with the human chromosome 3p22-p21.3. Two nonallelic mouse mutants, tippy and ducky, with severe neurological phenotypes map to the vicinity of the Mobp locus. We therefore tested whether MOBP malfu nction could explain the tippy and ducky defects. In tippy mutant anim als, MOBP expression and that of other myelin markers were indistingui shable from wild type. The ultrastructure of tippy myelin was shown to be normal. Ducky animals showed a slight reduction of the brain size, most evident in the spinal cord, but normal progress of myelination. Both MOBP and myelin basic protein expression were lowered only region ally in the CNS, but were mostly normal in the anterior parts of the b rain. Ultrastructurally, ducky myelin appeared normal. MOBP transcript sizes and the molecular weights of the encoded proteins were shown to be normal in both mutants. Finally, the nucleotide sequence of the ab undant MOBP-81 cDNA was determined and compared with tippy and ducky M OBP-81. Wild-type mouse MOBP-81 protein was 99% identical to the rat h omologue, and tippy and ducky MOBP-81 were identical to the wild-type sequence. Our results suggest that alterations in the Mobp gene are no t the cause for the severe neurological phenotypes of ducky and tippy mice.