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Science 19 May 2000:
Vol. 288. no. 5469, pp. 1248 - 1251
DOI: 10.1126/science.288.5469.1248
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Reports

A Mutation in PRKAG3 Associated with Excess Glycogen Content in Pig Skeletal Muscle

Denis Milan, 1* Jin-Tae Jeon, 2* Christian Looft, 3 Valerie Amarger, 2 Annie Robic, 1 Mattias Thelander, 4 Claire Rogel-Gaillard, 5 Sven Paul, 3 Nathalie Iannuccelli, 1 Lars Rask, 6 Hans Ronne, 4 Kerstin Lundström, 7 Norbert Reinsch, 3 Joel Gellin, 1 Ernst Kalm, 3 Pascale Le Roy, 8 Patrick Chardon, 5 Leif Andersson 2dagger

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 gamma  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.

1 Laboratoire de Génétique Cellulaire, Institut National de la Recherche Agronomique (INRA), 31326 Castanet-Tolosan, France.
2 Department of Animal Breeding and Genetics,
4 Department of Plant Biology,
7 Department of Food Science, Swedish University of Agricultural Sciences, Box 597, SE-751 24 Uppsala, Sweden.
3 Institute of Animal Breeding and Husbandry, Christian-Albrechts-University, 24098 Kiel, Germany.
5 Laboratoire de Radiobiologie et d'Etude du Génome, CEA INRA and
8 Station de Génétique Quantitative et Appliquée, INRA, 78352 Jouy en Josas Cedex, France.
6 Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, SE-752 23 Uppsala, Sweden.
*   These authors contributed equally to the work.

dagger    To whom correspondence should be addressed. E-mail: Leif.Andersson{at}bmc.uu.se

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