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Rescue of Calcineurin Aα−/−Mice Reveals a Novel Role for the α Isoform in the Salivary Gland
- Source :
- American Journal of Pathology; April 2011, Vol. 178 Issue: 4 p1605-1613, 9p
- Publication Year :
- 2011
-
Abstract
- Calcineurin is an important signal transduction mediator in T cells, neurons, the heart, and kidneys. Recent evidence points to unique actions of the two main isoforms of the catalytic subunit. Although the β isoform is required for T-cell development, α is important in the brain and kidney. In addition, mice lacking α but not β suffer from failure to thrive and early mortality. The purpose of this study was to identify the cause of postnatal death of calcineurin α null (CnAα−/−) mice and to determine the mechanism of α activity that contributes to the phenotype. CnAα−/−mice and wild-type littermate controls were fed a modified diet and then salivary gland function and histology were examined. In vitrostudies were performed to identify the mechanism of α action. Data show that calcineurin is required for normal submandibular gland function and secretion of digestive enzymes. Loss of α does not impair nuclear factor of activated T-cell activity or expression but results in impaired protein trafficking downstream of the inositol trisphosphate receptor. These findings show a novel function of calcineurin in digestion and protein trafficking. Significantly, these data also provide a mechanism to rescue to adulthood a valuable animal model of calcineurin inhibitor-mediated neuronal and renal toxicities.
Details
- Language :
- English
- ISSN :
- 00029440
- Volume :
- 178
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- American Journal of Pathology
- Publication Type :
- Periodical
- Accession number :
- ejs23565954
- Full Text :
- https://doi.org/10.1016/j.ajpath.2010.12.054