The average life expectancy of individuals bearing this mutation is about 35 years. We have made mice bearing mutations in these two different genes. Both strains of mice are viable and have been followed for at least 30 weeks. Their blood pressure and heart rates are normal or near normal. These animals have been studied by echocardiography and do not develop significant cardiac hypertrophy until age 30 weeks.
Older mice have more histologic evidence of disease than younger mice.
Cardiac function of these animals has been measured both in anesthetized mice and in isolated hearts. The Arg403Gln mutation reduces cardiac output as well as maximum left ventricular pressure and maximum rate of relaxation in male mice but not female mice. The alteration in the relaxation phase may be due to hemodynamic obstruction or physical obstruction of the flow of blood out of the left ventricle. Alternatively, it may be due to altered myocardial performance due to altered cardiac muscle function. Eventually these mouse strains should allow us to distinguish between these models.