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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Animals, Heart, Heart Defects, Congenital, Heart Ventricles, Humans, Mice, Knockout, Myosin Heavy Chains, Nonmuscle Myosin Type IIB, Point Mutation.
user
Does a point mutation in Myh10 cause major defects in heart development and body wall closure? Context: The 3 isoforms of nonmuscle myosin (NM) II (NMII-A, NMII-B, and NMII-C) play various roles during mouse embryonic development. Previous work, using knockout and hypomorphic mice, showed that Myh10 encoding myosin heavy chain II-B is critical for cardiac and brain development. Ablating or decreasing NMII-B by 80% results in cardiac (ventricular septal defect, double outlet of the right ventricle) and brain defects but not midline fusion defects. Neither NMII-A nor II-C seems to play roles in early myocardial development. We had previously generated point mutant knock-in mice and now report novel findings as a result of expressing motor-deficient NMII-B at wild-type levels. Homozygous mice die at embryonic day 14.5 in cardiac failure, exhibiting abnormalities not seen in NMII-B null and hypomorphic mice: a failure in midline fusion resulting in a cleft palate, ectopia cordis, and a large omphalocele. Fusion of the sternum and endocardial cushions is impaired in the mutant mice associated with a failure in apoptosis of the mesenchymal cells. Failure to disassemble myocyte cell-cell adhesions during cardiac outflow tract development contributes to impaired outflow tract myocardialization and displacement of the aorta to the right ventricle.
assistant
Expression of motor-impaired NMII-B disrupts normal ventral body wall closure because of a dominant-negative effect. This is not because of the loss of NMII-B function but rather a gain-of-function resulting from prolonged cross-linking of NMII-B to actin filaments, thereby interfering with the dynamics of actomyosin cytoskeletal structure. Furthermore, impaired NMII-B motor activity inhibits outflow tract myocardialization, leading to mislocalization of the aorta. Final Decision: yes