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P27 knockout mice: reduced myostatin in muscle and altered adipogenesis
Ji Lin1, Mary Anne Della-Fera, Changlong Li
1Department of Animal & Dairy Science and Foods and Nutrition, University of Georgia, 444 Animal Science Complex, Athens, GA 30602-2771, USA.
Abstract:
Knockout of the P27(kip) gene, which encodes a cyclin-dependent kinase inhibitor involved in cell proliferation regulation, results in growth enhancement in mice. To investigate how p27 deficiency affected adipogenesis and myogenesis, levels of PPARgamma, C/EBPalpha, and the myogenesis inhibitor, myostatin, were measured in p27(-/-) (n=14), p27(+/-) (n=18), and p27(+/+) mice (n=11). Body weight and gastrocnemius muscle (GC) mass were increased in p27(-/-) mice (P<0.05), but there were no differences in fat depot weights, percent body fat or serum leptin concentrations among genotypes. PPARgamma, but not C/EBPalpha, was markedly increased in p27(-/-) mice (P<0.05). There was also a higher incidence of inguinal fat apoptosis (P<0.01) in p27(-/-) mice. Myostatin levels were reduced in GC muscle of p27(-/-) mice (P<0.05). These findings suggest that in p27 deficient mice, increased skeletal muscle mass is mediated in part through decreased myostatin. Although total adiposity was not changed, increased PPARgamma levels suggest an alteration in adipogenesis.
Insights
Mice lacking the P27 gene showed enhanced growth, with increased skeletal muscle mass linked to reduced myostatin. Adipogenesis markers were altered, despite no change in overall body fat.
Area of Science:
- Molecular Biology
- Genetics
- Physiology
Background:
- The P27 gene (kip) encodes a cyclin-dependent kinase inhibitor crucial for regulating cell proliferation.
- P27 deficiency in mice leads to overall growth enhancement.
- Understanding p27's role in adipogenesis and myogenesis is essential for metabolic and muscle research.
Purpose of the Study:
- To investigate the impact of p27 deficiency on adipogenesis and myogenesis in mice.
- To analyze the expression of key regulatory proteins: PPARgamma, C/EBPalpha, and myostatin.
- To correlate P27 gene knockout with changes in body composition and muscle mass.
Main Methods:
- Analysis of p27 knockout (p27(-/-)), heterozygous (p27(+/-)), and wild-type (p27(+/+)) mice.
- Measurement of body weight, gastrocnemius muscle mass, and fat depot weights.
- Quantification of PPARgamma, C/EBPalpha, and myostatin levels; assessment of inguinal fat apoptosis and serum leptin.
Main Results:
- p27(-/-) mice exhibited significantly increased body weight and gastrocnemius muscle mass.
- PPARgamma levels were markedly elevated in p27(-/-) mice, suggesting altered adipogenesis.
- Myostatin levels were reduced in the gastrocnemius muscle of p27(-/-) mice, correlating with increased muscle mass.
Conclusions:
- Increased skeletal muscle mass in p27-deficient mice is partly mediated by decreased myostatin.
- Elevated PPARgamma suggests alterations in adipogenesis pathways, despite unchanged overall adiposity.
- P27 plays a significant role in balancing skeletal muscle and adipose tissue development.