A chaperone in motoneuron disease

Mice with the progressive motor neuronopathy (pmn) mutation develop a degenerative and fatal motoneuron disease shortly after birth, making them a popular animal model for studying human neurodegenerative diseases such as spinal muscular atrophy. Two independent reports (Bömmel et al., page 563; Martin, N., et al. 2002. Nat. Genet. 32:443–447) now identify the genetic defect in pmn mice as a point mutation in a gene for a tubulin-specific chaperone. The result suggests that motoneuron axons, which can reach lengths of greater than one meter in adult humans, may put unusual demands on the microtubule cytoskeleton.

Fine-scale mapping and sequencing revealed a single missense mutation in the Tbce gene in pmn mice, resulting in the substitution of tryptophan for glycine in the tubulin-specific chaperone protein CofE. The wild-type glycine residue is strictly conserved among vertebrates, raising the...