Objective To explore the effect of PRKAG2 gene G100S mutation in cystathionine β-synthase (CBS) region on adenosine monophosphate-activated protein kinase (AMPK) activity in cardiomyocytes of mice.Methods A human PRKAG2 (G100S) transgenic mouse model was established. Four-week-old and 12-week-old transgenic mice, and 4-week-old and 12-weekold wildtype littermate were randomly selected from N4 generation mice (n=6). The activity of AMPK in mouse cardiomyocytes was detected by phosphorylation assay kit. The difference of AMPK activity was compared between transgenic mice and wildtype littermate, and the changes of the activity of AMPK with the increase of age were observed in transgenic mice.Results The AMPK activities in cardiomyocytes of 4-week-old and 12-week-old transgenic mice were significantly lower than those of the wildtype littermate (0.042±0.013 vs 0.063±0.013, and 0.032±0.008 vs 0.062±0.018), and the differences were significant (P=0.019, P=0.004). There was no significant difference in the AMPK activity of cardiomyocytes between 4-week-old and 12-weekold transgenic mice (P=0.135).Conclusion The PRKAG2 gene G100S mutation can cause a reduction of AMPK activity in cardiomyocytes of transgenic mice, and AMPK activity does not significantly increase or decrease with the growth of the transgenic mice.