c-Abl tyrosine kinase regulates cardiac growth and development

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 backgrou...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-01, Vol.107 (3), p.1136-1141
Main Authors: Qiu, Zhaozhu, Cang, Yong, Goff, Stephen P
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Cell cycle
Cell growth
Cell Proliferation
Cyclins
Embryos
Gene expression regulation
Genes, Lethal
Genetic mutation
Genotype & phenotype
Heart
Heart - growth & development
Hyperplasia
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Mutation
Myocardium
Phenotype
Physical growth
Proteins
Proto-Oncogene Proteins c-abl - genetics
Proto-Oncogene Proteins c-abl - metabolism
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0913131107