| First Author | Madsen K | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 4 | Pages | e62503 |
| PubMed ID | 23638102 | Mgi Jnum | J:200874 |
| Mgi Id | MGI:5509441 | Doi | 10.1371/journal.pone.0062503 |
| Citation | Madsen K, et al. (2013) Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin Aalpha null mice. PLoS One 8(4):e62503 |
| abstractText | Mice lacking the alpha isoform of the catalytic subunit of calcineurin (CnAalpha) were first reported in 1996 and have been an important model to understand the role of calcineurin in the brain, immune system, bones, muscle, and kidney. Research using the mice has been limited, however, by failure to thrive and early lethality of most null pups. Work in our laboratory led to the rescue of CnAalpha-/- mice by supplemental feeding to compensate for a defect in salivary enzyme secretion. The data revealed that, without intervention, knockout mice suffer from severe caloric restriction. Since nutritional deprivation is known to significantly alter development, it is imperative that previous conclusions based on CnAalpha-/- mice are revisited to determine which aspects of the phenotype were attributable to caloric restriction versus a direct role for CnAalpha. In this study, we find that defects in renal development and function persist in adult CnAalpha-/- mice including a significant decrease in glomerular filtration rate and an increase in blood urea nitrogen levels. These data indicate that impaired renal development we previously reported was not due to caloric restriction but rather a specific role for CnAalpha in renal development and function. In contrast, we find that rather than being hypoglycemic, rescued mice are mildly hyperglycemic and insulin resistant. Examination of muscle fiber types shows that previously reported reductions in type I muscle fibers are no longer evident in rescued null mice. Rather, loss of CnAalpha likely alters insulin response due to a reduction in insulin receptor substrate-2 (IRS2) expression and signaling in muscle. This study illustrates the importance of re-examining the phenotypes of CnAalpha-/- mice and the advances that are now possible with the use of adult, rescued knockout animals. |
