MOLECULAR ANALYSIS OF GLIAL-CELL DEVELOPMENT IN THE CANINE SHAKING PUP MUTANT

The shaking pup, a canine mutant, carries a point mutation in the myel in proteolipid protein (PLP) gene that causes dysmyelination of the ce ntral 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 develo pmental patterns of expression similar to those observed in the contro ls, but at significantly reduced levels. Expression of the genes for t he major CNS myelin proteins, PLP and the myelin basic protein, are mo st dramatically affected in the shaking pup, although reduced expressi on levels are observed for other oligodendrocyte-specific genes such a s 2',3'-cyclic nucleotide 3'phosphodiesterase and glucose phosphate de hydrogenase. The pattern of gene expression in the shaking pup indicat es that the oligodendrocytes experience an inhibition in development a fter the myelination program has begun. There appears to be little evi dence for an astrocytic response to the dysmyelinating condition at th e RNA level, but we present evidence for ectopic expression of PO mRNA in the CNS. Expression of the PO and PLP genes in the sciatic nerve a ppears to be normal, reinforcing previous reports that PNS myelination is unaffected by the mutation in the PLP gene.