A Mutation in <i>PRKAG3</i> Associated with Excess Glycogen Content in Pig Skeletal Muscle

TLDR

The RN‑ mutation in PRKAG3, prevalent in Hampshire pigs, elevates skeletal‑muscle glycogen, improving meat content but reducing processing yield, and parallels yeast SNF4 loss‑of‑function glycogen‑storage defects. The study aims to analyze the PRKAG3 signaling pathway to better understand muscle physiology and the pathogenesis of type‑2 diabetes. The mutation is a nonconservative R200Q substitution in the PRKAG3 gene encoding the muscle‑specific γ subunit of AMPK.

Abstract

A high proportion of purebred Hampshire pigs carries the dominant RN − mutation, which causes high glycogen content in skeletal muscle. The mutation has beneficial effects on meat content but detrimental effects on processing yield. Here, it is shown that the mutation is a nonconservative substitution (R200Q) in the PRKAG3 gene, which encodes a muscle-specific isoform of the regulatory γ subunit of adenosine monophosphate–activated protein kinase (AMPK). Loss-of-function mutations in the homologous gene in yeast ( SNF4 ) 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 mellitus in humans, a metabolic disorder associated with impaired glycogen synthesis.