Journal article
Cardiomyocyte-Specific Expression of Lamin A Improves Cardiac Function in Lmna−/− Mice
PloS one, Vol.7(8), e42918
08/15/2012
DOI: 10.1371/journal.pone.0042918
PMCID: PMC3419749
PMID: 22905185
Abstract
Lmna−/− 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−/− mice. We observed increased total desmin protein levels and disorganization of the cytoplasmic desmin network in ∼20% of Lmna−/− ventricular myocytes, rescued in a cell-autonomous manner in Lmna−/− mice expressing a cardiac-specific lamin A transgene (Lmna−/−; Tg). Lmna−/−; Tg mice displayed significantly increased contractility and preservation of myocardial performance compared to Lmna−/− mice. Lmna−/−; Tg mice attenuated ERK1/2 phosphorylation relative to Lmna−/− mice, potentially underlying the improved localization of connexin43 to the intercalated disc. Electrocardiographic recordings from Lmna−/− mice revealed arrhythmic events and increased frequency of PR interval prolongation, which is partially rescued in Lmna−/−; Tg mice. These findings support our observation that Lmna−/−; Tg mice have a 12% median extension in lifespan compared to Lmna−/− mice. While significant, Lmna−/−; Tg mice only have modest improvement in cardiac function and survival likely stemming from the observation that only 40% of Lmna−/−; Tg cardiomyocytes have detectable lamin A expression. Cardiomyocyte-specific restoration of lamin A in Lmna−/− mice improves heart-specific pathology and extends lifespan, demonstrating that the cardiac pathology of Lmna−/− 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
Details
- Title: Subtitle
- Cardiomyocyte-Specific Expression of Lamin A Improves Cardiac Function in Lmna−/− Mice
- Creators
- Richard L FrockSteven C ChenDao-Fu DaEllie FrettCarmen LauChristina BrownDiana N PakYuexia WangAntoine MuchirHoward J WormanLuis F SantanaWarren C LadigesPeter S RabinovitchBrian K Kennedy
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.7(8), e42918
- DOI
- 10.1371/journal.pone.0042918
- PMID
- 22905185
- PMCID
- PMC3419749
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; San Francisco, USA
- Alternative title
- Cardiac Rescue of Lmna−/− Mice
- Language
- English
- Date published
- 08/15/2012
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Radiation Oncology
- Record Identifier
- 9984070354302771
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