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Translation elongation factor eEF1A2 is essential for post-weaning survival in mice
H J Newbery1, D H Loh1, J E O'Donoghue1
1Medical Genetics, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom and.
The Journal of Biological Chemistry
|July 21, 2007
Summary
Loss of translation elongation factor eEF1A2 causes abnormalities in wasted mice. New antibodies reveal eEF1A2 expression in unexpected tissues, clarifying the genetic basis of the wasted mouse phenotype.
Area of Science:
- Molecular Biology
- Genetics
- Neuroscience
Background:
- Translation elongation factor eEF1A has two variants: eEF1A1 (ubiquitous) and eEF1A2 (muscle/brain restricted).
- Specific antibodies for variant analysis were previously unavailable.
- Wasted mice (wst/wst) possess a deletion affecting eEF1A2, but impact on neighboring genes was unknown.
Purpose of the Study:
- To generate specific antibodies for eEF1A1 and eEF1A2 variant analysis.
- To determine the precise expression patterns of eEF1A1 and eEF1A2.
- To elucidate the role of eEF1A2 in the phenotype of wasted mice.
Main Methods:
- Generation of anti-peptide antibodies specific to eEF1A1 and eEF1A2.
- Immunohistochemical analysis of eEF1A1 and eEF1A2 expression in various tissues.
- Transgenic experiments to assess gene expression changes in wasted mice.
Main Results:
- eEF1A2 is highly expressed in pancreatic islet cells and enteroendocrine cells, previously thought to lack expression.
- eEF1A1 and eEF1A2 expression patterns are generally mutually exclusive.
- Wasted mouse phenotype, including motor neuron degeneration, correlates with eEF1A1/eEF1A2 expression imbalance; immune abnormalities stem from a stress response.
Conclusions:
- Loss of eEF1A2 function is the sole cause of abnormalities in wasted mice.
- The study clarifies the tissue-specific expression of eEF1A2 and its critical role.
- New antibodies enable accurate analysis of eEF1A1 and eEF1A2 expression.
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