A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle

A high proportion of purebred Hampshire pigs carries the dominant RN- mutat ion, which causes high glycogen content in skeletal muscle. The mutation ha s beneficial effects on meat content but detrimental effects on processing yield. Here, it is shown that the mutation is a nonconservative substitutio n (R200Q) in the PRKAG3 gene, which encodes a muscle-specific isoform of th e regulatory gamma subunit of adenosine monophosphate-activated protein kin ase (AMPK). Loss-of-function mutations in the homologous gene in yeast (SNF 4) cause defects in glucose metabolism, including glycogen storage. Further analysis of the PRKAG3 signaling pathway may provide insights into muscle physiology as well as the pathogenesis of noninsulin-dependent diabetes mel litus in humans, a metabolic disorder associated with impaired glycogen syn thesis.