Partial correction of abnormal cardiac development in caspase-8-deficient mice by cardiomyocyte expression of p 35.

Baculovirus p 35 protein protects cells from apoptotic cell death by inhibiting caspase activation. We have established transgenic mouse lines specifically expressing p 35 in cardiomyocytes, and primary cardiomyocytes isolated from these mice exhibit resistance to staurosporine-induced apoptosis. In a previous study, we observed defects in heart formation associated with abdominal hemorrhage and cardiomyocyte cell death in caspase-8-deficient animals. In order to better understand the etiology of the cardiac defects and embryonic lethality in caspase-8-deficient mice, we crossed these mice with the p 35 transgenic animals. Although the newly generated mice still died in utero and exhibited some cardiac defects, cardiomyocyte apoptosis was suppressed and ventricular trabeculation was restored. Thus, cardiomyocyte expression of p 35 prevented cell death induced by staurosporine or caspase-8 deficiency. Additionally, our data suggest that caspase-8 plays multiple roles in cardiac development.