Chapter 32 The molecular basis of the neuropathies of mouse and human

Abstract

Publisher Summary This chapter discusses the discovery of a gene for peripheral myelin protein 22 (PMP22) and its involvement in trembler neurological mutants. The cDNA for PMP22 was found in three independent library screens, two comparing the cDNAs from libraries made from normal rat sciatic nerve and from sciatic nerve after injury and the other comparing the cDNAs of quiescent and proliferating fibroblasts. In the latter instance, the gene was referred to as the growth arrest specific gene-3 because of its potential involvement in controlling growth in these cells. The cDNA encodes a small, extremely hydrophobic protein of 160 amino acid residues, with four putative membrane spanning domains and one asparagine-linked glycosylation site. Expression of PMP22 correlates with myelin formation and myelin-specific gene expression during sciatic nerve development and its down-regulation after nerve injury follows that of the myelin protein Po. In situ hybridization confirmed that PMP22 mRNA is synthesized by Schwann cells. PMP22 mRNA expression is clearly regulated by axon contact and is found mainly in the peripheral nervous system (PNS). The chapter discusses PMP22 and the inherited peripheral neuropathies in human, along with human peripheral neuropathies associated with mutations in other PNS myelin genes.