Molecular basis of canine muscle type phosphofructokinase deficiency.
Muscle type phosphofructokinase (M-PFK) deficiency is a rare inherited glycogen storage disease in humans that causes exertional myopathy and hemolysis. The molecular basis of canine M-PFK deficiency, the only naturally occurring animal homologue, was investigated. Lack of M-PFK enzyme activity was caused by a nonsense mutation in the penultimate exon of the M-PFK gene, leading to rapid degradation of a truncated (40 amino acids) and therefore unstable M-PFK protein. A polymerase chain reaction-based test was devised to identify M-PFK-deficient and carrier animals. This represents one of only a few inborn errors of metabolism where the molecular defect has been identified in a large animal model which can now be used to develop and assess novel therapeutic strategies.
Smith
B F
BF
Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6010, USA.
Stedman
H
H
Rajpurohit
Y
Y
Henthorn
P S
PS
Wolfe
J H
JH
Patterson
D F
DF
Giger
U
U
D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006008:Glycogen Storage Disease / Q000235:genetics*; D006579:Heterozygote; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology*; D010375:Pedigree; D010732:Phosphofructokinase-1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D010732:Phosphofructokinase-1