title: Missense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease.
abstract: Progressive 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 E (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 alpha-tubulin and beta-tubulin heterodimeric complexes. Isolated motoneurons from pmn mutant mice exhibit shorter axons and axonal swelling with irregularly structured beta-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.
authors.affiliation: Institute of Clinical Neurobiology, University of Würzburg, 97080 Würzburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bommel
authors.forename: Gang
authors.initials: G
authors.lastname: Xie
authors.forename: Wilfried
authors.initials: W
authors.lastname: Rossoll
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiese
authors.forename: Sibylle
authors.initials: S
authors.lastname: Jablonka
authors.forename: Thomas
authors.initials: T
authors.lastname: Boehm
authors.forename: Michael
authors.initials: M
authors.lastname: Sendtner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D048429:Cell Size; D002470:Cell Survival; D002878:Chromosomes, Human, Pair 1; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016472:Motor Neuron Disease / Q000235:genetics* / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology; D020125:Mutation, Missense; D010375:Pedigree; D016415:Sequence Alignment
chemical_list: D018832:Molecular Chaperones; C469269:Tbce protein, mouse