Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article PDF (Full Text) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                      What's this?

Mutant spinal neurons (right) have shorter, swollen axons.

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 possibility that a similar defect may be responsible for some of the unexplained sporadic cases of human motoneuron diseases.

After identifying the mutation, Bömmel et al. isolated and cultured motoneurons from embryonic pmn and wild-type mice, and found that the mutant neurons grow shorter axons and exhibit axonal swellings. The pmn motoneurons appear to survive as well as wild-type motoneurons, suggesting that the condition seen in the mutant mice is a consequence of axonal defects rather than neuronal death.

The findings suggest a relatively straightforward explanation for the pmn phenotype: a defective microtubule chaperone protein could interfere with the proper assembly of the microtubule heterodimers required for normal axonal transport, leading to shorter axons. Microtubules are also essential for fundamental cellular processes such as mitotic spindle assembly, so it is unclear how pmn mutant mice manage to develop normally. One possibility is that neuron-specific isoforms of tubulin may have a more stringent requirement for CofE during assembly.

Alan W. Dove

alanwdove{at}earthlink.net

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Article

Missense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease

Heike Bömmel, Gang Xie, Wilfried Rossoll, Stefan Wiese, Sibylle Jablonka, Thomas Boehm, and Michael Sendtner
J. Cell Biol. 2002 159: 563-569. [Abstract] [Full Text] [PDF]

This Article PDF (Full Text) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                      What's this?