Effects of Increased Dosage of the Plp Gene: A Study in Transgenic Mice

Abstract

The Plp gene encodes two proteins (proteolipid protein and DM20), by alternative splicing of the primary transcript, that between them account for greater than 50% of total myelin protein in the central nervous system. Though the proteolipid protein is thought to have a structural role in the compaction of the myelin sheath the role of the DM20 protein isoform remains uncertain but is speculated to involve oligodendrocyte development. The Plp gene has been strongly conserved during evolution, and across species, and it is well recognised that its mutation is involved with dysmyelination. It has become increasingly clear that as well as mutations altering the nucleotide sequence being associated with disease that duplications of the gene locus, without nucleotide changes, are also significant in disease aetiopathogenesis in man. This project describes the phenotypic consequences of extra copies of the Plp gene on two lines of transgenic mice (#66 and #72) in relation to myelin gene expression