title: Depletion of lamina-associated polypeptide 1 from cardiomyocytes causes cardiac dysfunction in mice.
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.
authors.affiliation: Department of Medicine; College of Physicians & Surgeons; Columbia University; New York, NY USA; Department of Pathology and Cell Biology; College of Physicians & Surgeons; Columbia University; New York, NY USA.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Department of Medicine; College of Physicians & Surgeons; Columbia University; New York, NY USA; Department of Pathology and Cell Biology; College of Physicians & Surgeons; Columbia University; New York, NY USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Dour
authors.affiliation: Department of Medicine; College of Physicians & Surgeons; Columbia University; New York, NY USA.
authors.forename: Fusako
authors.initials: F
authors.lastname: Sera
authors.affiliation: Department of Medicine; College of Physicians & Surgeons; Columbia University; New York, NY USA.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Iwata
authors.affiliation: Department of Medicine; College of Physicians & Surgeons; Columbia University; New York, NY USA.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Homma
authors.affiliation: Department of Medicine; College of Physicians & Surgeons; Columbia University; New York, NY USA.
authors.forename: Leroy C
authors.initials: LC
authors.lastname: Joseph
authors.affiliation: Department of Medicine; College of Physicians & Surgeons; Columbia University; New York, NY USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Morrow
authors.affiliation: Department of Neurology; University of Michigan Medical School; Ann Arbor, MI USA; Department of Cell and Developmental Biology; University of Michigan Medical School; Ann Arbor, MI USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Dauer
authors.affiliation: Department of Medicine; College of Physicians & Surgeons; Columbia University; New York, NY USA; Department of Pathology and Cell Biology; College of Physicians & Surgeons; Columbia University; New York, NY USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Worman
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009687:Nuclear Proteins
keywords: LAP1; cardiomyopathy; inner nuclear membrane; nuclear envelope; nuclear lamins