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Translation elongation factor eEF1A2 is essential for post-weaning survival in mice

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)28951-9
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number39
DOIs
StatePublished - 2007

Abstract

Translation elongation factor eEF1A, formerly known as EF-1 alpha, exists as two variant forms; eEF1A1, which is almost ubiquitously expressed, and eEF1A2, whose expression is restricted to muscle and brain at the level of whole tissues. Expression analysis of these genes has been complicated by a general lack of availability of antibodies that specifically recognize each variant form. Wasted mice (wst/wst) have a 15.8-kilobase deletion that abolishes activity of eEF1A2, but before this study it was unknown whether the deletion also affected neighboring genes. We have generated a panel of anti-peptide antibodies and used them to show that eEF1A2 is expressed at high levels in specific cell types in tissues previously thought not to express this variant, such as pancreatic islet cells and enteroendocrine cells in colon crypts. Expression of eEF1A1 and eEF1A2 is shown to be generally mutually exclusive, and we relate the expression pattern of eEF1A2 to the phenotype seen in wasted mice. We then carried out a series of transgenic experiments to establish whether the expression of other genes is affected by the deletion in wasted mice. We show that aspects of the phenotype such as motor neuron degeneration relate precisely to the relative expression of eEF1A1 and eEF1A2, whereas the immune system abnormalities are likely to result from a stress response. We conclude that loss of eEF1A2 function is solely responsible for the abnormalities seen in these mice.

    Research areas

  • Animals, Base Sequence, Colon, Gene Expression Regulation, Humans, Immune System, Insulin-Secreting Cells, Mice, Mice, Mutant Strains, Mice, Transgenic, Motor Neuron Disease, Organ Specificity, Peptide Elongation Factor 1, Protein Isoforms, Sequence Deletion, Wasting Syndrome, Weaning

ID: 458973