Uncoupling of hypomyelination and glial cell death by a mutation in the proteolipid protein gene.

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.. 
