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, Michael Sendtner

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Pogressive motor neuronopathy (pmn) mutant mice have been widely used as a model for human motoneuron disease. Mice that are homozygous for the pmn gene defect appear healthy at birth but develop progressive motoneuron disease, resulting in severe skeletal muscle weakness and respiratory failure by postnatal week 3. The disease starts at the motor endplates, and then leads to axonal loss and finally to apoptosis of the corresponding cell bodies. We localized the genetic defect in pmn mice to a missense mutation in the tubulin-specific chaperone (Tbce) gene on mouse chromosome 13. The human orthologue maps to chromosome 1q42.3. The Tbce gene encodes a protein (cofactor E) that is essential for the formation of primary α-tubulin and β-tubulin heterodimeric complexes. Isolated motoneurons from pmn mutant mice exhibit shorter axons and axonal swelling with irregularly structured-tubulin and tau immunoreactivity. Thus, the pmn gene mutation provides the first genetic evidence that alterations in tubulin assembly lead to retrograde degeneration of motor axons, ultimately resulting in motoneuron cell death.

Original languageEnglish (US)
Pages (from-to)563-569
Number of pages7
JournalJournal of Cell Biology
Volume159
Issue number4
DOIs
StatePublished - Nov 25 2002

Keywords

  • Motoneuron disease
  • Motor axon
  • PMN
  • Tubulin
  • Tubulin-specific chaperone E

ASJC Scopus subject areas

  • Cell Biology

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