Pfkm Knockout mouse models

Skeletal muscle glycolytic capacity rests on Pfkm, the mouse ortholog of human PFKM, which encodes the muscle subunit of phosphofructokinase 1 and dominates the tetramer in that tissue, where it catalyzes the committed, effectively irreversible ATP-dependent phosphorylation of fructose 6-phosphate and integrates AMP, ATP, citrate and fructose 2,6-bisphosphate signals into glycolytic rate. Recessive loss causes Tarui disease, glycogen storage disease type VII, in which exercise intolerance, cramps, myoglobinuria and compensated hemolysis follow from blocked muscle glycolysis, with the erythrocyte phenotype partial rather than complete because red cells contain M and L hybrid tetramers. Model design follows that tissue logic: a germline or muscle-restricted conditional null reproduces the metabolic myopathy, while patient-matched missense or splice knockins model residual activity and milder late-onset forms. Redundancy with Pfkl and Pfkp is real outside muscle. Choose the allele by endpoint, whether exercise challenge, glycogen accumulation, phosphorus magnetic resonance spectroscopy or hemolytic indices are the primary measures.

Pfkm null animals are straightforward to genotype and phenotype when survival is acceptable. They remain a standard background for pharmacology, biomarker, and rescue studies.