Muscle-specific AMPK beta 1 beta 2-null mice display a myopathy due to loss of capillary density in nonpostural muscles
Melissa M Thomas, David C Wang, Donna M D'Souza, Matthew P Krause, Andrew S Layne, David S Criswell, Hayley M O'Neill, Michael K Connor, Judy E Anderson, Bruce E Kemp, Gregory R Steinberg, Thomas J Hawke
The FASEB Journal | FEDERATION AMER SOC EXP BIOL | Published : 2014
AMP-activated protein kinase (AMPK) is a master regulator of metabolism. While muscle-specific AMPK β1β2 double-knockout (β1β2M-KO) mice display alterations in metabolic and mitochondrial capacity, their severe exercise intolerance suggested a secondary contributor to the observed phenotype. We find that tibialis anterior (TA), but not soleus, muscles of sedentary β1β2M-KO mice display a significant myopathy (decreased myofiber areas, increased split and necrotic myofibers, and increased centrally nucleated myofibers. A mitochondrial- and fiber-type-specific etiology to the myopathy was ruled out. However, β1β2M-KO TA muscles displayed significant (P<0.05) increases in platelet aggregation a..View full abstract
The 10F5 antibody developed by C. Lucas was obtained from the Developmental Studies Hybridoma Bank, developed under the auspices of the U.S. National Institute of Child Health and Human Development and maintained by the Department of Biology, University of Iowa (Iowa City, IA, USA). These studies were supported by grants and fellowships from the Natural Science and Engineering Research Council of Canada (T.J.H., G.R.S.) and the Canadian Institutes of Health Research (CIHR; T.J.H., G.R.S.), the Canadian Foundation for Innovation (T.J.H., G. R. S.), the Australian Research Council (B. E. K.), and the Australian National Health and Medical Research Council (B. E. K., G. R. S.). This work was supported, in part, by the Victorian government's Operational Infrastructure Support program (B. E. K.). G. R. S. holds a Canada Research Chair in Metabolism and Obesity. The authors also acknowledge the contributions of the Michael DeGroote Fellowship (M. M. T.), the Ontario Graduate Scholarship program (M. P. K.), and the Canadian Institutes of Health Research Banting and Best Doctoral Fellowship program (D. M. D.).