Journal Article

The <i>proteolipid protein</i> gene and myelin disorders in man and animal models

Donald A. Yool, Julia M. Edgar, Paul Montague and Sue Malcolm

in Human Molecular Genetics

Volume 9, issue 6, pages 987-992
Published in print April 2000 | ISSN: 0964-6906
Published online April 2000 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/9.6.987
The proteolipid protein gene and myelin disorders in man and animal models

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The two proteins, proteolipid protein and DM20, which are encoded by alternative transcripts from the proteolipid protein (PLP) gene, are major components of central nervous system myelin. In man, mutations of these proteins cause Pelizaeus–Merzbacher disease (PMD), an X-linked dysmyelinating neuropathy. The mutations found are very varied, ranging from deletions, loss-of-function and missense mutations to additional copies of the gene. This same range of known genetic defects has been observed in animal models with spontaneous and engineered Plp gene mutations. The relationship between genotype and phenotype is remarkably close in the animal models and the PMD cases, making them useful models for studying the mechanisms of PLP gene-related disease. As a result, it has become clear that the PLP gene plays a wider role in neural development in addition to its function as a structural component of myelin. It has also emerged that duplications of the PLP gene are the commonest mutation in PMD. Genetic disorders arising from a dosage effect may be more common than previously recognized. The study of the PLP gene in this rare disorder is, therefore, contributing both to our understanding of neural development and maintenance and to the mechanisms of human genetic disorders.

Journal Article.  5219 words.  Illustrated.

Subjects: Genetics and Genomics

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