A missense mutation in Tbce causes progressive motor neuronopathy in mice - PubMed (original) (raw)
doi: 10.1038/ng1016. Epub 2002 Oct 21.
Affiliations
- PMID: 12389029
- DOI: 10.1038/ng1016
A missense mutation in Tbce causes progressive motor neuronopathy in mice
Natalia Martin et al. Nat Genet. 2002 Nov.
Abstract
Mice that are homozygous with respect to the progressive motor neuronopathy (pmn) mutation (chromosome 13) develop a progressive caudio-cranial degeneration of their motor axons from the age of two weeks and die four to six weeks after birth. The mutation is fully penetrant, and expressivity does not depend on the genetic background. Based on its pathological features, the pmn mutation has been considered an excellent model for the autosomal recessive proximal childhood form of spinal muscular atrophy (SMA). Previously, we demonstrated that the genes responsible for these disorders were not orthologous. Here, we identify the pmn mutation as resulting in a Trp524Gly substitution at the last residue of the tubulin-specific chaperone e (Tbce) protein that leads to decreased protein stability. Electron microscopy of the sciatic and phrenic nerves of affected mice showed a reduced number of microtubules, probably due to defective stabilization. Transgenic complementation with a wildtype Tbce cDNA restored a normal phenotype in mutant mice. Our observations indicate that Tbce is critical for the maintenance of microtubules in mouse motor axons, and suggest that altered function of tubulin cofactors might be implicated in human motor neuron diseases.
Similar articles
- Golgi Fragmentation in ALS Motor Neurons. New Mechanisms Targeting Microtubules, Tethers, and Transport Vesicles.
Haase G, Rabouille C. Haase G, et al. Front Neurosci. 2015 Dec 8;9:448. doi: 10.3389/fnins.2015.00448. eCollection 2015. Front Neurosci. 2015. PMID: 26696811 Free PMC article. Review. - Missense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease.
Bommel H, Xie G, Rossoll W, Wiese S, Jablonka S, Boehm T, Sendtner M. Bommel H, et al. J Cell Biol. 2002 Nov 25;159(4):563-9. doi: 10.1083/jcb.200208001. J Cell Biol. 2002. PMID: 12446740 Free PMC article. - Auditory development in progressive motor neuronopathy mouse mutants.
Volkenstein S, Brors D, Hansen S, Berend A, Mlynski R, Aletsee C, Dazert S. Volkenstein S, et al. Neurosci Lett. 2009 Nov 6;465(1):45-9. doi: 10.1016/j.neulet.2009.09.006. Epub 2009 Sep 6. Neurosci Lett. 2009. PMID: 19735697 - Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome.
Parvari R, Hershkovitz E, Grossman N, Gorodischer R, Loeys B, Zecic A, Mortier G, Gregory S, Sharony R, Kambouris M, Sakati N, Meyer BF, Al Aqeel AI, Al Humaidan AK, Al Zanhrani F, Al Swaid A, Al Othman J, Diaz GA, Weiner R, Khan KT, Gordon R, Gelb BD; HRD/Autosomal Recessive Kenny-Caffey Syndrome Consortium. Parvari R, et al. Nat Genet. 2002 Nov;32(3):448-52. doi: 10.1038/ng1012. Epub 2002 Oct 21. Nat Genet. 2002. PMID: 12389028 - Parathyroid development and the role of tubulin chaperone E.
Parvari R, Diaz GA, Hershkovitz E. Parvari R, et al. Horm Res. 2007;67(1):12-21. doi: 10.1159/000095944. Epub 2006 Sep 27. Horm Res. 2007. PMID: 17008776 Review.
Cited by
- The wobbler mouse, an ALS animal model.
Moser JM, Bigini P, Schmitt-John T. Moser JM, et al. Mol Genet Genomics. 2013 Jun;288(5-6):207-29. doi: 10.1007/s00438-013-0741-0. Epub 2013 Mar 29. Mol Genet Genomics. 2013. PMID: 23539154 Free PMC article. Review. - TBCE Mutations Cause Early-Onset Progressive Encephalopathy with Distal Spinal Muscular Atrophy.
Sferra A, Baillat G, Rizza T, Barresi S, Flex E, Tasca G, D'Amico A, Bellacchio E, Ciolfi A, Caputo V, Cecchetti S, Torella A, Zanni G, Diodato D, Piermarini E, Niceta M, Coppola A, Tedeschi E, Martinelli D, Dionisi-Vici C, Nigro V, Dallapiccola B, Compagnucci C, Tartaglia M, Haase G, Bertini E. Sferra A, et al. Am J Hum Genet. 2016 Oct 6;99(4):974-983. doi: 10.1016/j.ajhg.2016.08.006. Epub 2016 Sep 22. Am J Hum Genet. 2016. PMID: 27666369 Free PMC article. - Golgi Fragmentation in ALS Motor Neurons. New Mechanisms Targeting Microtubules, Tethers, and Transport Vesicles.
Haase G, Rabouille C. Haase G, et al. Front Neurosci. 2015 Dec 8;9:448. doi: 10.3389/fnins.2015.00448. eCollection 2015. Front Neurosci. 2015. PMID: 26696811 Free PMC article. Review. - Neurobiology of axonal transport defects in motor neuron diseases: Opportunities for translational research?
De Vos KJ, Hafezparast M. De Vos KJ, et al. Neurobiol Dis. 2017 Sep;105:283-299. doi: 10.1016/j.nbd.2017.02.004. Epub 2017 Feb 22. Neurobiol Dis. 2017. PMID: 28235672 Free PMC article. Review. - The Microtubule Regulatory Protein Stathmin Is Required to Maintain the Integrity of Axonal Microtubules in Drosophila.
Duncan JE, Lytle NK, Zuniga A, Goldstein LS. Duncan JE, et al. PLoS One. 2013 Jun 26;8(6):e68324. doi: 10.1371/journal.pone.0068324. Print 2013. PLoS One. 2013. PMID: 23840848 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases