Document Detail


Progressive loss of motor neuron function in wasted mice: effects of a spontaneous null mutation in the gene for the eEF1 A2 translation factor.
MedLine Citation:
PMID:  15835265     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Wasted (wst) is a spontaneous autosomal recessive mutation in which the gene encoding translation factor eEF1A2 is deleted. Homozygous mice show tremors and disturbances of gait shortly after weaning, followed by motor neuron degeneration, paralysis, and death by about 28 days. We have now conducted a more detailed analysis of neuromuscular pathology in these animals. Reactive gliosis was observed at 19 days postnatal in wst/wst cervical spinal cord, showing a rostrocaudal gradient. This was followed a few days later by motor neuron vacuolation and neurofilament accumulation, again with a rostrocaudal progression. Thoracic/abdominal muscles from wst/wst mice aged 17 days showed evidence of progressive denervation of motor endplates, including weak synaptic transmission and retraction of motor nerve terminals. Similar abnormalities appeared in distal, lumbrical muscles from about 25 days of age. We conclude that spontaneous failure of eEF1A2 expression in the wasted mutant first triggers gliosis in spinal cord and retraction of motor nerve terminals in muscle, and then motor neuron pathology and death. The early initiation and rapid progression of motor unit degeneration in wst/wst mice suggest that they should be considered an important and accessible model of early-onset motor neuron degeneration in humans.
Authors:
Helen J Newbery; Thomas H Gillingwater; Permphan Dharmasaroja; Josephine Peters; Stephen B Wharton; Derek Thomson; Richard R Ribchester; Catherine M Abbott
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuropathology and experimental neurology     Volume:  64     ISSN:  0022-3069     ISO Abbreviation:  J. Neuropathol. Exp. Neurol.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-19     Completed Date:  2005-05-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985192R     Medline TA:  J Neuropathol Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  295-303     Citation Subset:  IM    
Affiliation:
Medical Genetics, Molecular Medicine Center, University of Edinburgh, Western General Hospital, Edinburgh, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Electrophysiology
Humans
Mice
Motor Neurons / cytology,  metabolism*,  pathology*
Muscle, Skeletal / innervation,  pathology
Mutation*
Neuromuscular Junction / metabolism,  pathology
Peptide Elongation Factor 1 / genetics*,  metabolism*
Rotarod Performance Test
Wasting Syndrome* / genetics,  pathology
Chemical
Reg. No./Substance:
0/EEF1A2 protein, human; 0/Eef1a2 protein, mouse; 0/Peptide Elongation Factor 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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