Effect of the Truncated cTnC Expression on Cardiac Function in Transgenic Fish / 利用基因轉殖魚研究cardiactroponinC異常對心臟功能的影響

碩士 / 國立臺灣大學 / 分子與細胞生物學研究所 / 94 / Mutations of cardiac troponin C (cTnC) may cause cardiomyopathy, which is one of the most serious heart diseases of elders, but there is no suitable animal model to study this late-onset disorder. Zebrafish is a good material due to its embryo is transparent and the inducible system in vivo is developed. Zebrafish inducible transgenic line was carried out which expressed cardiac specific EGFP and truncated cTnC at the same time with doxcycline (10μg/ml) induction. After induction at 3 dpf of F2 embryo, we observed that the heart beating rate of zebrafish inducible transgenic line was slower than that of the control fish (188.9± 21.7 Vs. 199.8±22.2 beats/min) after 4 days induction. Both the diastolic volume and the systolic volume of zebrafish inducible transgenic line were larger than control group over the observation time (after 1 to 6 days induction). Furthermore, the ejection fraction of zebrafish inducible transgenic line was also lower than control group during the observation period (after 1 to 6 days induction), especially at 5 days induction (8 dpf) (41.9±6.8 % Vs. 49.3±5.7 %).On the other hand, most of the individuals revealed progressively dilated atrium syndrome till 6-9 days induction, and the individuals with syndrome would die soon. And we found the myocardium wall of ventricle of zebrafish inducible transgenic line (D12) have ventricular muscle wall irregular thickening(5.4∼24.3μm).This phenotype is like the eccentric hypertrophy of human dilated cardiomyopathy. In conclusion, induction of heart-specific truncated form cTnC competing with normal cTnC activity would lead to increased end-diastolic ventricular volume、increased end-systolic ventricular volume、decreased ejection fraction and heart wall thickness disproportionate,these all are the symptom of dilated cardiomyopathy. We think that zebrafish inducible transgenic line is a potential animal model for cardiomyopathy research.

Identiferoai:union.ndltd.org:TW/094NTU05061014
Date January 2006
CreatorsChun-An Pai, 白峻安
Contributors蔡懷楨
Source SetsNational Digital Library of Theses and Dissertations in Taiwan
Languagezh-TW
Detected LanguageEnglish
Type學位論文 ; thesis
Format47

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