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 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.
Qiu
Zhaozhu
Z
Department of Microbiology, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Cang
Yong
Y
Goff
Stephen P
SP
D000818:Animals; D049109:Cell Proliferation; D005804:Genes, Lethal; D006321:Heart / Q000254:growth & development*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*
D016315:Proto-Oncogene Proteins c-abl