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The molecular genetics of myelination: An update
Author(s) -
Lemke Greg
Publication year - 1993
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.440070402
Subject(s) - biology , proteolipid protein 1 , myelin , gene , genetics , oligodendrocyte , peripheral myelin protein 22 , schwann cell , mutation , transgene , microbiology and biotechnology , gene knockin , embryonic stem cell , gene targeting , myelin basic protein , phenotype , neuroscience , central nervous system
Recent molecular genetic studies have provided new insights into the structure and function of 2 of the major integral membrane proteins of myelin—the proteolipid protein (PLP) and protein zero (P o )—and have uncovered a third such protein—PMP22/gas3. The rumpshaker mouse has been shown to carry a point mutation in the PLP gene that uncouples a deleterious effect on CNS myelin assembly, which these mice exhibit, from oligodendrocyte degeneration and cell death, which they do not. The developmental importance of the P o protein in PNS myelination has been dramatically demonstrated by the analysis of loss‐of‐function mutations engineered through the expression of antisense RNA and through the insertional inactivation of the P o gene by homologous recombination in embryonic stem cells and the generation of P o ‐deficient mice. The cloned promoter of the P o gene has been shown to drive quantitative, Schwann cell‐specific expression of heterologous genes in transgenic mice. The PMP22/gas3 gene, previously cloned from fibroblast cell lines, has been found to encode an axonally regulated Schwann cell protein that is assembled into PNS myelin. Importantly, this gene appears to be the target of mutations that result in the Trembler alleles in mice, and in Charcot‐Marie‐Tooth disease Type 1a, the most common inherited peripheral neuropathy in humans.