Cardiac troponin I gene knockout: A mouse model of myocardial troponin I deficiency

XuPei Huang, YeQing Pi, Kevin J. Lee, Anne S. Henkel, Ronald G. Gregg, Patricia A. Powers, Jeffery W. Walker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalCirculation research
Issue number1
StatePublished - Jan 8 1999


  • Cardiac development
  • Heart failure
  • Ischemia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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