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Journal of Neuroscience, Vol 10, 117-124, Copyright © 1990 by Society for Neuroscience

ARTICLE

Conservative amino acid substitution in the myelin proteolipid protein of jimpymsd mice

S Gencic and LD Hudson
Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurologic Disorders and Stroke, Bethesda, Maryland 20892.

The capacity for synthesizing and maintaining a compact myelin sheath is destroyed in a number of inborn errors of myelin metabolism. One class of hypomyelinating mutations, which displays an X-linked pattern of inheritance, is distinguished by marked disturbances in oligodendrocyte differentiation. We have defined the molecular defect in one such mutant that lacks mature oligodendrocytes, the X-linked jimpy myelin synthesis deficient (jpmsd) trait in mice. The structure of the gene encoding the most abundant myelin protein, proteolipid protein (PLP), was determined by mapping and partially sequencing genomic clones from jpmsd and wild-type mice. Jpmsd mice have a single base change in PLP, a C----T transition in exon 6 that would substitute a valine for alanine in both PLP and its alternatively spliced isoform, DM20. The mutation was confirmed by polymerase chain reaction- amplifying exon 6 from genomic DNA and then either sequencing the amplified DNA or directly probing exon 6 with oligonucleotides designed to detect a single base mismatch. The conservative amino acid replacement in PLP/DM20 of jpmsd mice results in a pleiotropic phenotype similar to that observed for the allelic mutation jimpy, in which a splicing defect has radically altered the PLP/DM20 protein. The accelerated turnover of oligodendrocytes in both mouse mutants suggests a function for PLP/DM20 in oligodendrocyte differentiation distinct from the role of these proteolipid proteins as structural components of the myelin sheath.

This article has been cited by other articles:

				D. A. Yool, J. M. Edgar, P. Montague, and S. Malcolm The proteolipid protein gene and myelin disorders in man and animal models Hum. Mol. Genet., April 1, 2000; 9(6): 987 - 992. [Abstract] [Full Text] [PDF]

				M. Jung, I. Sommer, M. Schachner, and K.-A. Nave Monoclonal Antibody O10 Defines a Conformationally Sensitive Cell-Surface Epitope of Proteolipid Protein (PLP): Evidence that PLP Misfolding Underlies Dysmyelination in Mutant Mice J. Neurosci., December 15, 1996; 16(24): 7920 - 7929. [Abstract] [Full Text] [PDF]

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