SERCA2 Haploinsufficiency in a Mouse Model of Darier Disease Causes a Selective Predisposition to Heart Failure

Figure 5

Effects of Atp2a2 heterozygosity in a transgenic model of increased myofibrillar Ca²⁺ sensitivity. WT mice, mice expressing the Glu180Gly mutant -tropomyosin, which causes hypertrophic cardiomyopathy (HCM), and double mutant HCM/Atp2a2^+/− (HCM/HET) mice were analyzed. Survival of HCM and HCM/HET mice was assessed at 5 weeks of age (a). Gross morphometry at 4 weeks of age showed (b) overt remodeling, (c) increased heart weight : body weight ratios (HW : BW), and (d) increased ventricular weight : body weight ratios (VW : BW) in HCM/HET mice. RT-PCR shows elevated mRNA levels in HCM/HET hearts for (e) atrial natriuretic peptide (Nppa), (f) -myosin heavy chain (Myh7), (g) skeletal -actin (Acta1), and (h) connective tissue growth factor (Ctgf). mRNA levels were normalized to Gapdh expression. Values shown are means ± SE. = at least 4 for each genotype. versus HCM controls.

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