Characterized contractile phenotypes of transgenic mice in isolated papillary muscles

Objective: To characterize the cardiac contractile phenotypes of genetically engineered mice

Background: Mice are the most widely used species of genetically engineered animals, and many mouse lines may exhibit altered cardiac phenotypes. Although becoming more commonly available now, techniques for studying cardiac contractile phenotypes of mice are still technically demanding.

Methods: Left ventricular papillary muscles were isolated, inserted into W-shaped clamps made from platinum foil, mounted in a muscle chamber and stimulated through the platinum clamps at frequencies between 2 Hz and 6 Hz. The technique was used to characterize the phenotypes of mice overexpressing SERCA (sarcoplasmic reticulum Ca²⁺ ATPase), phospholamban knock-out mice, mice lacking thyroid hormone receptor (T₃R) isoforms a or b, and mice overexpressing a mutant human T₃Rb. The technique is particularly suitable for studying the time course of cardiac contraction, as well as the effects of parameters that are not easily altered in vivo such as stimulation frequency.

Results: SERCA overexpression accelerates cardiac relaxation and calcium transients (J. Clin. Invest. 100: 380-389, 1997. - ABSTRACT). Ablation of phospholamban inverts the cardiac force-frequency relationship (Am. J. Physiol. 278: H249-H255, 2000. - ABSTRACT). Overexpression of the mutant T₃Rb results in a hypothyroid phenotype despite normal T₃ levels (Endocrinol. 140: 897-902, 1999). Other results are being published.