Molecular analysis of glial cell development in the canine 'shaking pup' mutant.

Abstract

The shaking pup, a canine mutant, carries a point mutation in the myelin proteolipid protein (PLP) gene that causes dysmyelination of the central nervous system (CNS) with resultant tremor, seizures, and other persistent neurological deficits. The developmental potential of glial cells in the shaking pup CNS and peripheral nervous system (PNS) was evaluated by quantitative analysis of the expression of several glial-specific genes. All of the myelin-associated genes demonstrated developmental patterns of expression similar to those observed in the controls, but at significantly reduced levels. Expression of the genes for the major CNS myelin proteins, PLP and the myelin basic protein, are most dramatically affected in the shaking pup, although reduced expression levels are observed for other oligodendrocyte-specific genes such as 2',3'-cyclic nucleotide 3'phosphodiesterase and glucose phosphate dehydrogenase. The pattern of gene expression in the shaking pup indicates that the oligodendrocytes experience an inhibition in development after the myelination program has begun. There appears to be little evidence for an astrocytic response to the dysmyelinating condition at the RNA level, but we present evidence for ectopic expression of P0 mRNA in the CNS. Expression of the P0 and PLP genes in the sciatic nerve appears to be normal, reinforcing previous reports that PNS myelination is unaffected by the mutation in the PLP gene.