| First Author | Huang X | Year | 1999 |
| Journal | Circ Res | Volume | 84 |
| Issue | 1 | Pages | 1-8 |
| PubMed ID | 9915769 | Mgi Jnum | J:53628 |
| Mgi Id | MGI:1333026 | Doi | 10.1161/01.res.84.1.1 |
| Citation | Huang X, et al. (1999) Cardiac troponin I gene knockout: a mouse model of myocardial troponin I deficiency [see comments]. Circ Res 84(1):1-8 |
| abstractText | Troponin I is a subunit of the thin filament-associated troponin-tropomyosin complex involved in calcium regulation of skeletal and cardiac muscle contraction. We deleted the cardiac isoform of troponin I by using gene targeting in murine embryonic stem cells to determine the developmental and physiological effects of the absence of this regulatory protein. Mice lacking cardiac troponin I were born healthy, with normal heart and body weight, because a fetal troponin I isoform (identical to slow skeletal troponin I) compensated for the absence of cardiac troponin I. Compensation was only temporary, however, as 15 days after birth slow skeletal troponin I expression began a steady decline, giving rise to a troponin I deficiency. Mice died of acute heart failure on day 18, demonstrating that some form of troponin I is required for normal cardiac function and survival. Ventricular myocytes isolated from these troponin I-depleted hearts displayed shortened sarcomeres and elevated resting tension measured under relaxing conditions and had a reduced myofilament Ca sensitivity under activating conditions. The results show that (1) developmental downregulation of slow skeletal troponin I occurs even in the absence of cardiac troponin I and (2) the resultant troponin I depletion alters specific mechanical properties of myocardium and can lead to a lethal form of acute heart failure. |
