Depletion of lamina-associated polypeptide 1 from cardiomyocytes causes cardiac dysfunction in mice

Ji Yeon Shin, Caroline Le Dour, Fusako Sera, Shinichi Iwata, Shunichi Homma, Leroy C. Joseph, John P. Morrow, William T. Dauer, Howard J. Worman

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

We previously showed that striated muscle-selective depletion of lamina-associated polypeptide 1 (LAP1), an integral inner nuclear membrane protein, leads to profound muscular dystrophy with premature death in mice. As LAP1 is also depleted in hearts of these mice, we examined their cardiac phenotype. Striated muscle-selective LAP1 knockout mice display ventricular systolic dysfunction with abnormal induction of genes encoding cardiomyopathy related proteins. To eliminate possible confounding effects due to skeletal muscle pathology, we generated a new mouse line in which LAP1 is deleted in a cardiomyocyte-selective manner. These mice had no skeletal muscle pathology and appeared overtly normal at 20 weeks of age. However, cardiac echocardiography revealed that they developed left ventricular systolic dysfunction and cardiac gene expression analysis revealed abnormal induction of cardiomyopathy-related genes. Our results demonstrate that LAP1 expression in cardiomyocytes is required for normal left ventricular function, consistent with a report of cardiomyopathy in a human subject with mutation in the gene encoding LAP1.

Original languageEnglish (US)
JournalNucleus (United States)
Volume5
Issue number3
DOIs
StatePublished - May 23 2014
Externally publishedYes

Keywords

  • Cardiomyopathy
  • Inner nuclear membrane
  • LAP1
  • Nuclear envelope
  • Nuclear lamins

ASJC Scopus subject areas

  • Cell Biology

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    Shin, J. Y., Le Dour, C., Sera, F., Iwata, S., Homma, S., Joseph, L. C., Morrow, J. P., Dauer, W. T., & Worman, H. J. (2014). Depletion of lamina-associated polypeptide 1 from cardiomyocytes causes cardiac dysfunction in mice. Nucleus (United States), 5(3). https://doi.org/10.4161/nucl.29227