Developmental Expression of the P₀ Glycoprotein and Basic Protein mRNAs in Normal and Trembler Mutant Mice

Mice affected by the autosomal dominant Trembler mutation exhibit a severe hypomyelinization of the PNS. Previous biochemical studies have shown that the accumulation of the major PNS myelin proteins, P₀ and myelin basic protein (MBP), is strongly diminished in Trembler sciatic nerves during postnatal development. We performed Northern blots which showed that the size of mRNA species for P₀ and MBP in normal and mutant mice are indistinguishable. Densitometric analysis of Northern blots showed that, in normal mice, the proportion of P₀ mRNA increases up to the 12th day, then decreases slowly. At day 40, the proportion is 60% of the maximal value. In the mutant, the proportion of P₀ mRNA increases up to the 12th day and then decreases much faster than in the control. At days 12 and 40, the P₀ mRNA proportion measured in Trembler sciatic nerves rep resents only 40% and 7%, respectively, of the proportion measured in control littermates. The MBP mRNA proportion in the normal mice increases up to the 16th day, and then decreases to attain 45% of the maximum level at day 40. In the Trembler mouse, there is a maximum level at day 12, representing 25% of the normal level, but the MBP mRNA is barely detectable at days 8 or 40. Thus, these data seem to indicate that in the Trembler sciatic nerves, the proportions of P₀ and MBP mRNAs are too small to allow the synthesis of normal levels of the corresponding proteins.