Key Laboratory of Human Disease Comparative Medicine,Ministry of Heath
SHAO Hai-Tao ZHANG Li XIANG Zhi-Guang CHEN Wei ZHANG Xiao-Juan CAO Xing-Shui LV Dan, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Beijing 100021, China.
Objective To generate the heart-specific cTnIR145G expression transgenic mice and to determine the function and morphology of the mice. Methods The transgenic vector was constructed by inserting the human cTnIR145G gene into the down stream of α-MHC promoter. The transgenic mice were created by the method of microinjection. The genotype of the transgenic line was identified by PCR and the expression level of the gene was determined by Western blot. The death was recorded and the pathologic changes were analyzed with echocardiography, electrocardiography and light microscopy observation. Reasults Four lines of C57BL/6J transgenic mice with high levels of cTnIR145G expression were established. The mice of high expressed line mostly dead before mature. The heart of cTnIR145G transgenic mice showed decreased ventricular chamber, increased ventricular wall and percent fractional shortening (FS%) compared with the non-transgenic mice by echocardiography analysis. Ventricular repolarization dysfunction was determined by electrocardiography. Myocardial hypertrophy and myocyte disarray were observed by histological analysis. Conclusions The cTnIR145G transgenic mice give a similar pathological phenotype with the human familial hypertrophic cardiomyopathy (FHC). The transgenic mice could be an useful animal model for the research of the mechanisms of mutation in cTnI caused FHC.