| First Author | Ma X | Year | 2009 |
| Journal | Circ Res | Volume | 105 |
| Issue | 11 | Pages | 1102-9 |
| PubMed ID | 19815823 | Mgi Jnum | J:170148 |
| Mgi Id | MGI:4944049 | Doi | 10.1161/CIRCRESAHA.109.200303 |
| Citation | Ma X, et al. (2009) Conditional ablation of nonmuscle myosin II-B delineates heart defects in adult mice. Circ Res 105(11):1102-9 |
| abstractText | RATIONALE: 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. METHODS AND 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. |
