| First Author | Nadon NL | Year | 1990 |
| Journal | Development | Volume | 110 |
| Issue | 2 | Pages | 529-37 |
| PubMed ID | 1723945 | Mgi Jnum | J:75 |
| Mgi Id | MGI:48615 | Doi | 10.1242/dev.110.2.529 |
| Citation | Nadon NL, et al. (1990) A point mutation in the proteolipid protein gene of the 'shaking pup' interrupts oligodendrocyte development. Development 110(2):529-37 |
| abstractText | The differentiation of the oligodendrocyte from its bipotential progenitor culminates in the production of the myelin-specific proteins and the elaboration of membrane processes that ensheath the axon. Mutations in proteolipid protein (PLP) and its alternatively spliced isoform DM-20, the major protein constituents of central nervous system myelin, are characterized by a significant reduction in the number of mature oligodendrocytes, resulting in severe hypomyelination, tremor and early death. The canine shaking pup carries such a mutation, a single base change that substitutes a proline for a histidine near the first transmembrane region of PLP and DM-20. This mutation hinders oligodendrocyte differentiation, as evidence by a splicing pattern at the PLP locus characteristic of immature oligodendrocytes. The spliced transcript expressed earliest in development, DM-20, continues to be overexpressed in shaking pup oligodendrocytes. The disruption of the normal maturation schedule in these X-linked dysmyelinating disorders suggests that PLP or DM-20 plays a fundamental role in oligodendrocyte development. We propose that, while the more abundant PLP is the primary structural component of myelin, DM-20 may be critical to oligodendrocyte maturation. |
