The changes of the cardiac structure and function in cTnTR141W transgenic mice.
OBJECTIVE
To establish the transgenic mouse of cTnT(R141W) gene to make an animal model of dilated cardiomyopathy.


METHODS
A transgenic plasmid was constructed by inserting the cTnT(R141W) gene driven by the alpha-MHC promoter. The expression level of the gene was determined with Northern blotting. Pathologic changes were observed by light microscopy and transmission electronic microscopy and analyzed with echocardiography. The localization of the mutant human cTnT protein was detected by immunohistochemistry. The hypertrophy markers were analyzed by RT-PCR.


RESULTS
Transgenic mice carrying the cTnT(R141W) mutation were established. The cTnT(R141W) was expressed by 1.5- to 2.0-fold that of the endogenous cTnT gene and was showed to assemble in the sarcomere. The transgenic heart exhibited a thinner ventricular wall and an enlarged ventricular chamber. Interstitial fibrosis and the elongated and lysed myofrils were also observed in the transgenic heart tissue. The function on EF%, FS% and movement of the ventricular wall was significantly decreased. The immature death occurred after 4 months of age and the immature death rate was 11.1% before 8 months of age in the cTnT(R141W) mice. The increased NPPB, ACTA1 and decreased ATP2A2 were detected in the transgenic heart.


CONCLUSIONS
The expression of mutant cTnT(R141W) in the mouse heart caused ventricular chamber enlargement, systolic dysfunction, myocardial hypertrophy, and interstitial fibrosis, suggesting that the cTnT(R141W) gene is a causal factor for DCM and that the cTnT(R141W) transgenic mouse is a useful animal model for the study of human DCM.
Juan
Feng
F
Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Comparative Medical Center, Peking Union Medical College, Beijing, China.
Wei
Dong
D
Xiongzhi
Quan
Q
Ran
Di
D
Chunmei
Ma
M
Lan
Huang
H
Chuan
Qin
Q
Lianfeng
Zhang
Z
D000818:Animals; D015152:Blotting, Northern; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D004452:Echocardiography; D015870:Gene Expression; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D019076:Transgenes