A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle.
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.
Milan
D
D
Laboratoire de Génétique Cellulaire, Institut National de la Recherche Agronomique (INRA), 31326 Castanet-Tolosan, France.
Jeon
J T
JT
Looft
C
C
Amarger
V
V
Robic
A
A
Thelander
M
M
Rogel-Gaillard
C
C
Paul
S
S
Iannuccelli
N
N
Rask
L
L
Ronne
H
H
Lundström
K
K
Reinsch
N
N
Gellin
J
J
Kalm
E
E
Roy
P L
PL
Chardon
P
P
Andersson
L
L
D055372:AMP-Activated Protein Kinases; D000483:Alleles; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D015971:Gene Expression Regulation, Enzymologic; D006003:Glycogen / Q000378:metabolism*; D006720:Homozygote; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid; D013552:Swine
D018076:DNA, Complementary; D007527:Isoenzymes; D006003:Glycogen; D011494:Protein Kinases; C526225:PRKAG3 protein, human; D055372:AMP-Activated Protein Kinases