Ablation and Mutation of Nonmuscle Myosin Heavy Chain II-B Results in a Defect in Cardiac Myocyte Cytokinesis

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Abstract
We have identified a novel form of cardiac myocyte enlargement in nonmuscle myosin heavy chain II-B (NMHC II-B) ablated mice, based on a partial failure in cytokinesis. In contrast to most cells, cardiac myocytes lack NMHC II-A, and ablation of NMHC II-B results in a heart with 70% fewer myocytes at embryonic day 14.5 (E14.5) than control mice (B+/B− and B+/B+). In addition, B−/B− cardiac myocytes show a marked increase in binucleation at E12.5, reflecting the occurrence of karyokinesis in the absence of cytokinesis. An increase in binucleation and cell size is also found in hypomorphic, homozygous mice harboring a single amino acid mutation (R709C) in the gene encoding NMHC II-B. The nonmyocytes in B−/B− hearts and homozygous mutant hearts, all of which contain NMHC II-A, do not show either of these abnormalities. B−/B− cardiac myocytes at E14.5 show a decreased bromodeoxyuridine (BrdU) labeling index compared with controls, consistent with the decrease in myocyte proliferation. This decreased BrdU label...