Myelin proteolipid protein gene expression in jimpy and jimpy(msd) mice.

Proteolipid protein (PLP) gene expression was studied in the dysmyelinating mouse mutant jimpy(msd) (jpmsd; myelin synthesis deficient) and compared with that in wild-type mice and the allelic mutant, jimpy (jp). Southern analyses of genomic DNA from jpmsd mice revealed no major rearrangements of the PLP gene relative to the wild-type mouse PLP gene. PLP-specific mRNA levels were significantly reduced in these mutant mice, although both the 3.2- and 2.4-kilobase PLP-specific mRNAs were seen. Also, no size differences in either PLP or DM20 mRNAs were found by S1 nuclease assays of brain RNA from either jpmsd or wild-type mice. Both PLP and DM20 protein were detectable at low levels in jpmsd brain homogenates, and these proteins comigrated with PLP and DM20 protein from normal mice. Western analyses showed an altered PLP:DM20 ratio in jpmsd mice relative to wild-type mice; DM20 levels exceeded PLP levels. It is surprising that a similar pattern of expression was seen in normal mice at less than 10 days of age: DM20 protein expression preceding PLP expression. Thus, jpmsd mice are capable of synthesizing normal PLP and DM20 protein; however, the PLP gene defect has affected the normal developmental pattern of expression for these two proteins.