UNDERSTANDING GLIAL ABNORMALITIES ASSOCIATED WITH MYELIN DEFICIENCY IN THE JIMPY MUTANT MOUSE

Jimpy is a shortened life-span murine mutant showing recessive sex-lin ked inheritance. The genetic defect consists of a point mutation in th e PLP gene and produces a severe CNS myelin deficiency that is associa ted with a variety of complex abnormalities affecting all glial popula tions. The myelin deficiency is primarily due to a failure to produce the normal amount of myelin during development. However, myelin destru ction and oligodendrocyte death also account for the drastic myelin de ficit observed in jimpy. The oligodendroglial cell line shows complex abnormalities in its differentiation pattern, including the degenerati on of oligodendrocytes through an apoptotic mechanism. Oligodendrocyte s seem to be the most likely candidate to be primarily altered in a di sorder affecting myelination, but disturbances affecting astrocytes an d microglia are also remarkable and may have a crucial significance in the development of the jimpy disorder. In fact, the jimpy phenotype m ay not be attributed to a defect in a single cell but rather to a defi ciency in the normal relations between glial cells. Evidences from a v ariety of sources indicate that the jimpy mutant could be a model for disturbed glial development in the CNS. The accurate knowledge of the significance of PLP and its regulation during development must be of v ital importance in order to understand glial abnormalities in jimpy, ( C) 1998 Elsevier Science B.V.