| First Author | Schneider A | Year | 1992 |
| Journal | Nature | Volume | 358 |
| Issue | 6389 | Pages | 758-61 |
| PubMed ID | 1380672 | Mgi Jnum | J:2126 |
| Mgi Id | MGI:50650 | Doi | 10.1038/358758a0 |
| Citation | Schneider A, et al. (1992) Uncoupling of hypomyelination and glial cell death by a mutation in the proteolipid protein gene. Nature 358(6389):758-61 |
| abstractText | Proteolipid protein (PLP; M(r) 30,000) is a highly conserved major polytopic membrane protein in myelin but its cellular function remains obscure. Neurological mutant mice can often provide model systems for human genetic disorders. Mutations of the X-chromosome-linked PLP gene are lethal, identified first in the jimpy mouse and subsequently in patients with Pelizaeus-Merzbacher disease. The unexplained phenotype of these mutations includes degeneration and premature cell death of oligodendrocytes with associated hypomyelination. Here we show that a new mouse mutant rumpshaker is defined by the amino-acid substitution Ile-to-Thr at residue 186 in a membrane-embedded domain of PLP. Surprisingly, rumpshaker mice, although myelin-deficient, have normal longevity and a full complement of morphologically normal oligodendrocytes. Hypomyelination can thus be genetically separated from the PLP-dependent oligodendrocyte degeneration. We suggest that PLP has a vital function in glial cell development, distinct from its later role in myelin assembly, and that this dichotomy of action may explain the clinical spectrum of Pelizaeus-Merzbacher disease. |
