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

Figure 4

Effects of Atp2a2 heterozygosity in a transgenic model of reduced myofibrillar Ca²⁺ sensitivity. WT mice, transgenic mice expressing the Glu154Lys mutant -tropomyosin, which causes dilated cardiomyopathy (DCM), and double mutant DCM/Atp2a2^+/− (DCM/HET) mice were analyzed. Morphometric analyses revealed similar heart weight : body weight (HW : BW) and heart weight : tibial length (HW : TL) ratios in DCM and DCM/HET mice (a); echocardiographic analysis shows fractional shortening and ejection fraction in DCM and DCM/HET mice (b); RT-PCR analysis shows mRNA levels for (c) atrial natriuretic peptide (Nppa), -myosin heavy chain (Myh7), and skeletal α-actin (Acta1) and for Atp2a2 (d). Immunoblot analysis of cardiac homogenates and quantitation show relative levels of SERCA2a (e) in DCM and DCM/HET hearts. mRNA levels were normalized to Gapdh and protein levels were normalized to sarcomeric actin (s.actin). Values are means ± SE. = at least 4 for each genotype. versus WT controls; versus WT controls; versus DCM; versus DCM.

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