A point mutation (R192H) in the C-terminus of human cardiac troponin I causes diastolic dysfunction in transgenic mice

J. Du, Chi Zhang, J. Liu, C. Sidky, X. P. Huang

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Cardiac troponin I (cTnI) mutations have been linked to the development of restrictive cardiomyopathy (RCM) in human patients. We modeled one mutation in human cTnI C-terminus, arginine192 → histidine (R192H) by cardiac specific expression of the mutated protein (cTnI193His in mouse sequence) in transgenic mice. Heart tissue sections revealed neither significant hypertrophy nor ventricular dilation in cTnI193His mice. The main functional alteration detected in cTnI193His mice by ultrasound cardiac imaging examinations was impaired cardiac relaxation manifested by a decreased left ventricular end diastolic dimension (LVEDD) and an increased end diastolic dimension in both atria. The cardiac ejection fraction (EF) was not significant changed in 6- to 8-week-old cTnI193His mice, however, the EF was significantly decreased in cTnI193His mice at age of 11 months. These data indicate that individual genetic conditions and environmental factors participate together in the development of the cTnI mutation based-cardiac muscle disorders. This mouse model provides us with a tool to further investigate the pathophysiology and the development of RCM.

Original languageEnglish
Pages (from-to)143-150
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume456
Issue number2
DOIs
StatePublished - Dec 15 2006
Externally publishedYes

Fingerprint

Troponin I
Point Mutation
Transgenic Mice
Restrictive Cardiomyopathy
Histidine
Mutation
Muscle
Ultrasonics
Tissue
Troponin C
Imaging techniques
Muscular Diseases
Hypertrophy
Dilatation
Ultrasonography
Myocardium
Proteins

Keywords

  • Diastolic dysfunction
  • Mutation
  • Restrictive cardiomyopathy
  • Transgenic mice
  • Troponin I
  • Ultrasound biomicroscopy

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

A point mutation (R192H) in the C-terminus of human cardiac troponin I causes diastolic dysfunction in transgenic mice. / Du, J.; Zhang, Chi; Liu, J.; Sidky, C.; Huang, X. P.

In: Archives of Biochemistry and Biophysics, Vol. 456, No. 2, 15.12.2006, p. 143-150.

Research output: Contribution to journalArticle

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