title: Conditional ablation of nonmuscle myosin II-B delineates heart defects in adult mice.
abstract: BACKGROUND
  Germline ablation of the cytoskeletal protein nonmuscle myosin II (NMII)-B results in embryonic lethality, with defects in both the brain and heart. Tissue-specific ablation of NMII-B by a Cre recombinase strategy should prevent embryonic lethality and permit study of the function of NMII-B in adult hearts.
  
  
  OBJECTIVE
  We sought to understand the function of NMII-B in adult mouse hearts and to see whether the brain defects found in germline-ablated mice influence cardiac development.
  
  
  RESULTS
  We used a loxP/Cre recombinase strategy to specifically ablate NMII-B in the brains or hearts of mice. Mice ablated for NMII-B in neural tissues die between postnatal day 12 and 22 without showing cardiac defects. Mice deficient in NMII-B only in cardiac myocytes (B(alphaMHC)/B(alphaMHC) mice) do not show brain defects. However, B(alphaMHC)/B(alphaMHC) mice display novel cardiac defects not seen in NMII-B germline-ablated mice. Most of the B(alphaMHC)/B(alphaMHC) mice are born with enlarged cardiac myocytes, some of which are multinucleated, reflecting a defect in cytokinesis. Between 6 to 10 months, they develop a cardiomyopathy that includes interstitial fibrosis and infiltration of the myocardium and pericardium with inflammatory cells. Four of 5 B(alphaMHC)/B(alphaMHC) hearts develop marked widening of intercalated discs.
  
  
  CONCLUSIONS
  By avoiding the embryonic lethality found in germline-ablated mice, we were able to study the function of NMII-B in adult mice and show that absence of NMII-B in cardiac myocytes results in cardiomyopathy in the adult heart. We also define a role for NMII-B in maintaining the integrity of intercalated discs.
authors.affiliation: Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Ma
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Takeda
authors.forename: Aman
authors.initials: A
authors.lastname: Singh
authors.forename: Zu-Xi
authors.initials: ZX
authors.lastname: Yu
authors.forename: Patricia
authors.initials: P
authors.lastname: Zerfas
authors.forename: Anthony
authors.initials: A
authors.lastname: Blount
authors.forename: Chengyu
authors.initials: C
authors.lastname: Liu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
authors.forename: Michael D
authors.initials: MD
authors.lastname: Schneider
authors.forename: Robert S
authors.initials: RS
authors.lastname: Adelstein
authors.forename: Qize
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000473:pathology; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D004195:Disease Models, Animal; D004452:Echocardiography; D005804:Genes, Lethal; D018095:Germ-Line Mutation; D006321:Heart / Q000196:embryology; D006849:Hydrocephalus / Q000235:genetics / Q000473:pathology; D019426:Integrases / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics* / Q000378:metabolism*
chemical_list: D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C045073:Cre recombinase; D019426:Integrases; D024501:Nonmuscle Myosin Type IIB