Gender influences cardiac function in the mdx model of Duchenne cardiomyopathy

Abstract

Aged mdx mice represent an important model for studying Duchenne cardiomyopathy. Herein we compared the cardiac phenotypes of 22-month-old male and female mdx mice. Surprisingly, only females displayed the characteristic cardiac dilation on pressure-volume loop analysis. Female mdx mice also exhibited lower contractility, larger Q waves, and higher ratios of heart weight to body weight. Our results reveal significant gender disparity in mdx cardiac function. Gender should be considered when using the mdx model for the study of Duchenne cardiomyopathy.

FIGURE 1

Heart disease in 22-month-old mdx mice is more severe in female mice than in male mice. (A) Representative PV loops from male BL10 and mdx mice. (B) Representative PV loops from female BL10 and mdx mice. (C) Baseline hemodynamic profiles (N = 15 for BL10 males, 16 for mdx males, 16 for BL10 females, 13 for mdx females). (D) ECG profiles (N = 13 for BL10 males, 11 for mdx males, 11 for BL10 females, 12 for mdx females). (E) Ratios of heart weight to body weight (N = 24 for BL10 males, 35 for mdx males, 24 for BL10 females, 44 for mdx females). (F) Hydroxyproline content (N = 7 for BL10 males, 18 for mdx males, 6 for BL10 females, 16 for mdx females). *mdx female significantly different from all other groups; ^#mdx male significantly different from all other groups; ^†significantly different from gender-matched group by t-test analysis; ^ˆBL10 male significantly greater than BL10 female; ^‡mdx groups are significantly different from BL10 groups by ANOVA analysis, but not from each other.