Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin Aα null mice.
Mice lacking the α isoform of the catalytic subunit of calcineurin (CnAα) 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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3640044?pdf=render |
| _version_ | 1811206902521004032 |
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| author | Kirsten Madsen Ramesh N Reddy S Russ Price Clintoria R Williams Jennifer L Gooch |
| author_facet | Kirsten Madsen Ramesh N Reddy S Russ Price Clintoria R Williams Jennifer L Gooch |
| author_sort | Kirsten Madsen |
| collection | DOAJ |
| description | Mice lacking the α isoform of the catalytic subunit of calcineurin (CnAα) 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 CnAα-/- 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 CnAα-/- mice are revisited to determine which aspects of the phenotype were attributable to caloric restriction versus a direct role for CnAα. In this study, we find that defects in renal development and function persist in adult CnAα-/- 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 CnAα 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 CnAα 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 CnAα-/- mice and the advances that are now possible with the use of adult, rescued knockout animals. |
| first_indexed | 2024-04-12T03:55:53Z |
| format | Article |
| id | doaj.art-30a7edb8faca479882499c57a469ef4d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T03:55:53Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-30a7edb8faca479882499c57a469ef4d2022-12-22T03:48:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6250310.1371/journal.pone.0062503Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin Aα null mice.Kirsten MadsenRamesh N ReddyS Russ PriceClintoria R WilliamsJennifer L GoochMice lacking the α isoform of the catalytic subunit of calcineurin (CnAα) 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 CnAα-/- 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 CnAα-/- mice are revisited to determine which aspects of the phenotype were attributable to caloric restriction versus a direct role for CnAα. In this study, we find that defects in renal development and function persist in adult CnAα-/- 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 CnAα 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 CnAα 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 CnAα-/- mice and the advances that are now possible with the use of adult, rescued knockout animals.http://europepmc.org/articles/PMC3640044?pdf=render |
| spellingShingle | Kirsten Madsen Ramesh N Reddy S Russ Price Clintoria R Williams Jennifer L Gooch Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin Aα null mice. PLoS ONE |
| title | Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin Aα null mice. |
| title_full | Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin Aα null mice. |
| title_fullStr | Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin Aα null mice. |
| title_full_unstemmed | Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin Aα null mice. |
| title_short | Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin Aα null mice. |
| title_sort | nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin aα null mice |
| url | http://europepmc.org/articles/PMC3640044?pdf=render |
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