Mutation in collagen gene induces cardiomyopathy in transgenic mice*

AbstractIn many remodeling tissues, such as the heart, collagen degradation to provide new integrin‐binding sites is required for survival. However, complete loss of integrin signaling due to disconnection from extracellular matrix (ECM) leads to apoptosis and dilatation. To test the hypothesis that a mutation in type I collagen gene induces cardiomyopathy, we employed a metalloproteinase‐resistant collagen mutant homozygous transgenic male (B6,129‐Colla‐1) and compared with age‐sex matched wildtype C57BL/J6 control mice. At the age of 38–42 weeks, aortic and left ventricle (LV) pressure were measured. The LV wall thickness and diameter were measured by a digital micrometer. The levels of matrix metalloproteinase‐2 (MMP‐2) activity and cardiospecific tissue inhibitor of metalloproteinase‐4 (TIMP‐4) were measured by zymography and Western blot analyses, respectively. The levels of collagenolysis were measured by Western blot using anti‐collagen antibody. In transgenic and wildtype mice, end‐diastolic pressure (EDP) was 8.3 ± 1.7 and 6.5 ± 1.1 mmHg; LV diameter was 3.43 ± 0.07 and 2.94 ± 0.05 mm; wall thickness was 1.18 ± 0.03 and 1.28 ± 0.04 mm; end‐diastolic wall stress was 600 ± 1