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C-Abl tyrosine kinase regulates cardiac growth and development.

ABSTRACT: The c-Abl protein is a ubiquitously expressed nonreceptor tyrosine kinase involved in the development and function of many mammalian organ systems, including the immune system and bone. Here we show that homozygous Abl mutant embryos and newborns on the C57BL/6J background, but not on other backgrounds, display dramatically enlarged hearts and die perinatally. The heart defects can be largely rescued by cardiomyocyte-specific restoration of the full-length c-Abl protein. The cardiac hyperplasia phenotype is not caused by decreased apoptosis, but rather by abnormally increased cardiomyocyte proliferation during later stages of embryogenesis. Genes involved in cardiac stress and remodeling and cell cycle regulation are also up-regulated in the mutant hearts. These findings reveal an essential role for c-Abl in mammalian heart growth and development.

SUBMITTER: Qiu Z

PROVIDER: S-EPMC2824287 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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c-Abl tyrosine kinase regulates cardiac growth and development.

Qiu Zhaozhu Z Cang Yong Y Goff Stephen P SP

Proceedings of the National Academy of Sciences of the United States of America 20091228 3

The c-Abl protein is a ubiquitously expressed nonreceptor tyrosine kinase involved in the development and function of many mammalian organ systems, including the immune system and bone. Here we show that homozygous Abl mutant embryos and newborns on the C57BL/6J background, but not on other backgrounds, display dramatically enlarged hearts and die perinatally. The heart defects can be largely rescued by cardiomyocyte-specific restoration of the full-length c-Abl protein. The cardiac hyperplasia ...[more]

PMID: 20080568

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