Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
PLoS One. 2012;7(7):e41917. doi: 10.1371/journal.pone.0041917. Epub 2012 Jul 25.
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.
翻译伸长因子同工型 eEF1A2 在肌肉和神经元中表达。eEF1A2 在小鼠中的缺失会导致神经退行性表型“浪费”（wst）。wst 突变的纯合子小鼠在出生后四周死于肌肉萎缩和神经退行性变。尽管该突变被认为是隐性的，但年龄较大的杂合子小鼠从未被详细检查过；最近已经表明，许多其他运动神经元退行性变的小鼠模型在杂合状态下也具有类似但不那么严重的表型异常。因此，我们研究了年龄对一组杂合子+/wst 小鼠和对照小鼠的影响，以确定预期的 eEF1A2 表达减少 50%是否与正常功能兼容。我们评估了握力测试作为在 3-4 周时区分浪费型和野生型小鼠的一种方法，然后在年龄较大的+/wst 和野生型小鼠中进行了相同的测试。我们还使用旋转棒性能和脊髓切片的免疫组织化学来评估老年杂合子小鼠的表型。尽管 eEF1A2 水平较低，但杂合子突变小鼠在神经肌肉功能或脊髓病理学迹象方面没有缺陷。
