Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK.
Biochem Soc Trans. 2009 Dec;37(Pt 6):1293-7. doi: 10.1042/BST0371293.
Translation elongation factor eEF1A (eukaryotic elongation factor 1A) exists as two individually encoded variants in mammals, which are 98% similar and 92% identical at the amino acid level. One variant, eEF1A1, is almost ubiquitously expressed, the other variant, eEF1A2, shows a very restricted pattern of expression. A spontaneous mutation was described in 1972, which gives rise to the wasted phenotype: homozygous wst/wst mice develop normally until shortly after weaning, but then lose muscle bulk, acquire tremors and gait abnormalities and die by 4 weeks. This mutation has been shown to be a deletion of 15 kb that removes the promoter and first exon of the gene encoding eEF1A2. The reciprocal pattern of expression of eEF1A1 and eEF1A2 in muscle fits well with the timing of onset of the phenotype of wasted mice: eEF1A1 declines after birth until it is undetectable by 3 weeks, whereas eEF1A2 expression increases over this time. No other gene is present in the wasted deletion, and transgenic studies have shown that the phenotype is due to loss of eEF1A2. We have shown that eEF1A2, but not eEF1A1, is also expressed at high levels in motor neurons in the spinal cord. Wasted mice develop many pathological features of motor neuron degeneration and may represent a good model for early onset of motor neuron disease. Molecular modelling of the eEF1A1 and eEF1A2 protein structures highlights differences between the two variants that may be critical for functional differences. Interactions between eEF1A2 and ZPR1 (zinc-finger protein 1), which interacts with the SMN (survival motor neuron) protein, may be important in motor neuron biology.
翻译伸长因子 eEF1A（真核伸长因子 1A）在哺乳动物中存在两种单独编码的变体，它们在氨基酸水平上的相似度为 98%，一致性为 92%。一种变体 eEF1A1 几乎普遍表达，另一种变体 eEF1A2 则表现出非常受限的表达模式。1972 年描述了一种自发突变，导致浪费表型：纯合子 wst/wst 小鼠在断奶后不久正常发育，但随后失去肌肉体积，出现震颤和步态异常，并在 4 周内死亡。该突变已被证明是 15kb 的缺失，该缺失去除了编码 eEF1A2 的基因的启动子和第一个外显子。eEF1A1 和 eEF1A2 在肌肉中的表达模式与浪费小鼠表型的发病时间非常吻合：eEF1A1 在出生后下降，直到 3 周时无法检测到，而 eEF1A2 的表达在此期间增加。浪费缺失中不存在其他基因，转基因研究表明该表型是由于 eEF1A2 的缺失所致。我们已经表明，eEF1A2（而不是 eEF1A1）在脊髓中的运动神经元中也以高水平表达。浪费小鼠表现出许多运动神经元退化的病理特征，可能是运动神经元疾病早期发病的良好模型。eEF1A1 和 eEF1A2 蛋白结构的分子建模突出了两种变体之间的差异，这些差异可能对功能差异至关重要。eEF1A2 与 ZPR1（锌指蛋白 1）之间的相互作用，与 SMN（运动神经元存活）蛋白相互作用，可能在运动神经元生物学中很重要。
