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Cardiac malformation in neonatal mice lacking connexin43
A G Reaume1, P A de Sousa, S Kulkarni
1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Science (New York, N.Y.)
|March 24, 1995
Summary
Connexin43 (Cx43) is vital for heart development, as its absence causes fatal birth defects. However, other connexins compensate, allowing fetal survival despite reduced cell communication.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cardiovascular Physiology
Background:
- Gap junctions, formed by connexin proteins, facilitate intercellular communication.
- Connexin43 (Cx43) is a major connexin protein in mammals.
- The role of Cx43 in heart development and function is not fully understood.
Purpose of the Study:
- To investigate the essential role of connexin43 (Cx43) in mammalian heart development.
- To determine the consequences of Cx43 absence on embryonic survival and cardiac function.
- To explore potential functional compensation by other connexins during fetal development.
Main Methods:
- Targeted mutagenesis was used to create Cx43-deficient mouse models.
- In vitro studies assessed dye coupling in mutant cell lines.
- In vivo analysis examined embryonic survival, cardiac morphology, and pulmonary function at birth.
Main Results:
- Cx43-deficient mouse embryos survived to term, but exhibited reduced dye coupling in vitro.
- Mutant embryos died at birth due to failure in pulmonary gas exchange.
- A swollen and blocked right ventricular outflow tract was observed in mutant hearts.
Conclusions:
- Cx43 plays a critical role in normal heart development, specifically in the right ventricular outflow tract.
- Complete absence of Cx43 leads to lethal cardiac defects incompatible with postnatal survival.
- Functional compensation by other connexins occurs in non-cardiac tissues during fetal development, enabling survival to term.