Correction: Cardiomyocyte-Specific Expression of Lamin A Improves Cardiac Function in Lmna−/−Mice

Lmna 2/2 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 Lmna 2/2 mice.We observed increased total desmin protein levels and disorganization of the cytoplasmic desmin network in ,20% of Lmna 2/2 ventricular myocytes, rescued in a cell-autonomous manner in Lmna 2/2 mice expressing a cardiac-specific lamin A transgene (Lmna 2/2 ; Tg).Lmna 2/2 ; Tg mice displayed significantly increased contractility and preservation of myocardial performance compared to Lmna 2/2 mice.Lmna 2/2 ; Tg mice attenuated ERK1/2 phosphorylation relative to Lmna 2/2 mice, potentially underlying the improved localization of connexin43 to the intercalated disc.Electrocardiographic recordings from Lmna 2/2 mice revealed arrhythmic events and increased frequency of PR interval prolongation, which is partially rescued in Lmna 2/2 ; Tg mice.These findings support our observation that Lmna 2/2 ; Tg mice have a 12% median extension in lifespan compared to Lmna 2/2 mice.While significant, Lmna 2/2 ; Tg mice only have modest improvement in cardiac function and survival likely stemming from the observation that only 40% of Lmna 2/2 ; Tg cardiomyocytes have detectable lamin A expression.Cardiomyocyte-specific restoration of lamin A in Lmna 2/2 mice improves heart-specific pathology and extends lifespan, demonstrating that the cardiac pathology of Lmna 2/2 mice limits survival.The expression of lamin A is sufficient to rescue certain cellular defects associated with loss of A-type lamins in cardiomyocytes in a cell-autonomous fashion.