Abstract
The expression of the proteolipid protein (PLP) gene of the myelin deficient (md) and normal rat was studied during the myelination period. The sizes of the PLP transcripts (1.6 and 3.2 kb) in the md and normal rat were identical although the md PLP messenger RNA level was extremely reduced as shown by in situ hybridization and Northern blot hybridization analysis. The structure of the md proteolipid protein gene was analyzed on the cDNA and genomic level. The molecular basis of the myelin deficiency phenotype has been elucidated: a point mutation in exon III (A---C transversion) verified by cDNA and genomic DNA sequencing causes a mutation of Thr75 to Pro and creates an additional AvaII restriction site in exon III of the md rat. The threonine to proline mutation located within the second transmembranal alpha-helix might induce a conformational change and thereby prohibit the integration of PLP into the membrane with the clinical manifestation of dysmyelination leading to premature death within 3-6 weeks.