Deletion of Akt1 causes heart defects and abnormal cardiomyocyte proliferation |
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| Authors: | Zai Chang Qiuting Feng Teng Teng Congjia Shan Brian A Hemmings Zhongzhou Yang |
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| Institution: | a MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center of Nanjing University, Nanjing, Chinab Department of Obstetrics and Gynecology, Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, Chinac Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland |
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| Abstract: | The PI3K-PDK1-PKB/Akt (PI3K, phosphoinositide-3 kinase; PDK1, phosphoinositide-dependent protein kinase 1; PKB, protein kinase B) signaling pathway plays a critical role in a variety of biological processes including cell survival, growth and proliferation, metabolism and organogenesis. Previously, we generated Akt1-deficient mice and found high neonatal mortality with unknown causes. Here we report that histological analysis of Akt1-deficient embryos and newborns revealed heart defects and decreased cell proliferation. Echocardiographic study of Akt1-deficient mice indicated decreased heart function. Further investigation revealed that Akt1 deficiency caused substantial activation of p38MAPK in the heart. Breeding the Akt1-deficient mice to mice that were heterozygous for a null p38α partially rescued the heart defects, significantly decreased post-natal mortality, and restored normal patterns of cardiomyocyte proliferation. Our study suggests that Akt1 is essential for heart development and function, in part, through suppression of p38MAPK activation. |
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| Keywords: | Akt/PKB knockout Heart defects p38 MAPK |
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