In vivo studies on nonmuscle myosin II expression and function in heart development.
Nonmuscle myosin II-B (NM II-B) plays an important role in cardiac development and function. Genetic ablation of NM II-B in mice results in both cellular and structural defects involving cardiac myocytes. These abnormalities include a ventricular septal defect, double outlet of the right ventricle, myocyte hypertrophy and premature onset of myocyte binucleation due to abnormalities in cytokinesis. The mice die by embryonic day (E) 14.5 due to defects in heart development. Conditional ablation of NM II-B in cardiac myocytes after E11.5 allows study of NM II-B function in adult myocytes. BaMHC/BaMHC mice are born with enlarged cardiac myocytes, some of which are multinucleated. Between 6-10 months of age they develop a cardiomyopathy. Many of these mice develop a marked widening of the intercalated discs. The loss of NM II-B from the intercalated discs primarily affects the adhesion junctions rather than the gap junctions and desmosomes. Interestingly, the loss of NM II-B results in a decrease in the actin binding protein mXin which also has been shown to cause disruption of the intercalated disc in addition to cardiac arrhythmias (Gustafson-Wagner et al. Am J Physiol Heart Circ Physiol. 2007, 293:H2680-92). Finally we review the evidence showing that ablation of NM II-C (which also localizes to the intercalated disc) in mouse hearts deficient in NM II-B expression results in destabilization of N-cadherin and beta-catenin in the intercalated disc.
Laboratory of Molecular Cardiology, NHLBI, National Institutes of Health, Bethesda, MD 20892, USA.
Xuefei
X
Ma
Robert S
RS
Adelstein
D000818:Animals; D005318:Fetal Heart / Q000196:embryology* / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008958:Models, Molecular; D009206:Myocardium / Q000378:metabolism; D024501:Nonmuscle Myosin Type IIB / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D020033:Protein Isoforms; D024501:Nonmuscle Myosin Type IIB