title: Haploinsufficiency for translation elongation factor eEF1A2 in aged mouse muscle and neurons is compatible with normal function.
abstract: Translation elongation factor isoform eEF1A2 is expressed in muscle and neurons. Deletion of eEF1A2 in mice gives rise to the neurodegenerative phenotype "wasted" (wst). Mice homozygous for the wasted mutation die of muscle wasting and neurodegeneration at four weeks post-natal. Although the mutation is said to be recessive, aged heterozygous mice have never been examined in detail; a number of other mouse models of motor neuron degeneration have recently been shown to have similar, albeit less severe, phenotypic abnormalities in the heterozygous state. We therefore examined the effects of ageing on a cohort of heterozygous +/wst mice and control mice, in order to establish whether a presumed 50% reduction in eEF1A2 expression was compatible with normal function. We evaluated the grip strength assay as a way of distinguishing between wasted and wild-type mice at 3-4 weeks, and then performed the same assay in older +/wst and wild-type mice. We also used rotarod performance and immunohistochemistry of spinal cord sections to evaluate the phenotype of aged heterozygous mice. Heterozygous mutant mice showed no deficit in neuromuscular function or signs of spinal cord pathology, in spite of the low levels of eEF1A2.
authors: Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
authors: Lowri A
authors: LA
authors: Griffiths
authors: Jennifer
authors: J
authors: Doig
authors: Antonia M D
authors: AM
authors: Churchhouse
authors: Faith C J
authors: FC
authors: Davies
authors: Charlotte E
authors: CE
authors: Squires
authors: Helen J
authors: HJ
authors: Newbery
authors: Catherine M
authors: CM
authors: Abbott
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001947:Breeding; D015536:Down-Regulation; D005260:Female; D018737:Hand Strength / Q000502:physiology; D057895:Haploinsufficiency; D006579:Heterozygote; D008297:Male; D051379:Mice; D009132:Muscles / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D020648:Peptide Elongation Factor 1 / Q000235:genetics*; D010641:Phenotype; D045442:Rotarod Performance Test; D013116:Spinal Cord / Q000166:cytology
chemical_list: C503235:Eef1a2 protein, mouse; D020648:Peptide Elongation Factor 1