cardiomyocyte-specific expression of lamin a improves cardiac function in lmna？？ micecardiomyocyte-specific核纤层蛋白的表达lmna改善心脏功能 老鼠.pdfVIP

Cardiomyocyte-Specific Expression of Lamin A Improves Cardiac Function in Lmna2/ 2 Mice 1 1 2 5 1 1 Richard L. Frock , Steven C. Chen , Dao-Fu Da , Ellie Frett , Carmen Lau , Christina Brown , 1 7 7 7 3 4 Diana N. Pak , Yuexia Wang , Antoine Muchir , Howard J. Worman , Luis F. Santana , Warren C. Ladiges , Peter S. Rabinovitch2, Brian K. Kennedy1,6* 1 Department of Biochemistry, University of Washington, Seattle, Washington, United States of America, 2 Department of Pathology, University of Washington, Seattle, Washington, United States of America, 3 Department of Physiology and Biophysics, University of Washington, Seattle, Washington, United States of America, 4 Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America, 5 Department of Pharmacology and Physiology, University of Rochester, Rochester, New York, United States of America, 6 Buck Institute for Age Research, Novato, California, United States of America, 7 Department of Medicine and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America Abstract Lmna2/ 2 mice display multiple tissue defects and die by 6–8 weeks of age reportedly from dilated cardiomyopathy with associated conduction defects. We sought to determine whether restoration of lamin A in cardiomyocytes improves cardiac function and extends the survival of Lmna2/ 2 mice. We observed increased total desmin protein levels and disorganization of the cytoplasmic desmin network in ,20% of Lmna2/ 2 ventricular myocytes, rescued in a cell-autonomous ma