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Nutritional Intervention Restores Muscle but Not Kidney Phenotypes in Adult Calcineurin Aα Null Mice
- Source :
- PLoS ONE, PLoS ONE, Vol 8, Iss 4, p e62503 (2013), Madsen, K, Reddy, R N, Price, S R, Williams, C R & Gooch, J L 2013, ' Nutritional intervention restores muscle but not kidney phenotypes in adult calcineurin aα null mice ', P L o S One, vol. 8, no. 4, pp. e62503 . https://doi.org/10.1371/journal.pone.0062503
- Publication Year :
- 2013
- Publisher :
- Public Library of Science, 2013.
-
Abstract
- 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.
- Subjects :
- Anatomy and Physiology
Mouse
Animal Nutrition
medicine.medical_treatment
lcsh:Medicine
Kidney
Mice
0302 clinical medicine
Molecular Cell Biology
Insulin
lcsh:Science
Musculoskeletal System
Animal Management
Mice, Knockout
0303 health sciences
Multidisciplinary
biology
Calcineurin
Animal Models
Slow-Twitch Muscle Fiber
medicine.anatomical_structure
Muscle Fibers, Slow-Twitch
Phenotype
Knockout mouse
Muscle
Genetic Engineering
Research Article
Biotechnology
Signal Transduction
medicine.medical_specialty
Signaling Pathways
03 medical and health sciences
Insulin resistance
Model Organisms
Internal medicine
medicine
Calcium-Mediated Signal Transduction
Animals
Muscle, Skeletal
Biology
030304 developmental biology
Caloric Restriction
Renal Physiology
lcsh:R
Renal System
medicine.disease
IRS2
Mice, Inbred C57BL
Insulin receptor
Endocrinology
biology.protein
lcsh:Q
Veterinary Science
Insulin Resistance
030217 neurology & neurosurgery
Gene Deletion
Transgenics
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....44a35f5b6131ffac50ef0ba5d14fda7b