Related Experiment Video
Updated: Aug 15, 2026
Improved Generation of Induced Cardiomyocytes Using a Polycistronic Construct Expressing Optimal Ratio of Gata4, Mef2c and Tbx5
Published on: November 13, 2015
Partial correction of abnormal cardiac development in caspase-8-deficient mice by cardiomyocyte expression of p 35
Nobuyuki Yajima1, Shu-Ichi Yamada, Takayuki Morisaki
1Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
Abstract:
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.
Insights
Baculovirus p35 protein prevents cardiomyocyte apoptosis, a key factor in heart development. This study shows p35 expression rescues cardiac defects and cell death in caspase-8 deficient mice.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cardiology
Background:
- Baculovirus p35 protein inhibits apoptosis by blocking caspase activation.
- Caspase-8 deficiency in mice leads to cardiac defects, embryonic lethality, and cardiomyocyte cell death.
- Previous studies indicated a role for caspase-8 in heart formation.
Purpose of the Study:
- To investigate the role of cardiomyocyte apoptosis in cardiac defects observed in caspase-8 deficient mice.
- To determine if p35 expression in cardiomyocytes can prevent apoptosis and rescue cardiac defects.
- To elucidate the function of caspase-8 in cardiac development.
Main Methods:
- Generation of transgenic mouse lines expressing baculovirus p35 protein in cardiomyocytes.
- Isolation and culture of primary cardiomyocytes from p35 transgenic mice.
- Induction of apoptosis using staurosporine.
- Crossing p35 transgenic mice with caspase-8 deficient mice.
- Analysis of cardiac morphology, cardiomyocyte apoptosis, and embryonic lethality.
Main Results:
- Primary cardiomyocytes from p35 transgenic mice showed resistance to staurosporine-induced apoptosis.
- Mice lacking caspase-8 but expressing p35 in cardiomyocytes still exhibited embryonic lethality and some cardiac defects.
- Cardiomyocyte apoptosis was suppressed in these double-mutant mice.
- Ventricular trabeculation was restored in the p35 expressing, caspase-8 deficient mice.
- Caspase-8 deficiency induced cardiomyocyte cell death, which was prevented by p35 expression.
Conclusions:
- Cardiomyocyte expression of p35 effectively prevents apoptosis induced by staurosporine or caspase-8 deficiency.
- Caspase-8 plays a critical role in preventing cardiomyocyte apoptosis during cardiac development.
- While p35 can suppress apoptosis, it does not fully rescue the embryonic lethality associated with caspase-8 deficiency, suggesting caspase-8 has multiple functions beyond apoptosis regulation in cardiac development.
