In vertebrates three genes, Myh9, Myh10 and Myh14 encode three different isoforms of the nonmuscle myosin II heavy chain (NMHC II). The motor activity of nonmuscle myosin II (NM II) resides in the N-terminal globular head domain and filament formation resides in the C-terminal rod domain. Previous work has shown that ablation of NM II-A in mice results in lethality by E6.5 with defects in cell-cell adhesion and a failure to produce a competent visceral endoderm. To understand the function of NM II-A during development we used homologous recombination to generate 4 different mouse lines:1-we replaced NM II-A with NM II-B by """"""""knocking in"""""""" cDNA encoding human NMHC II-B into the II-A locus, thereby ablating II-A and placing NMHC II-B under control of the endogenous II-A promoter (Ab*/Ab* mice). 2-we replaced endogenous NM II-A by knocking in two chimeric NMHCs, one encoding the N-terminal motor domain of NMHC II-A fused to the C-terminal II-B rod domain (Aab/Aab mice), 3-and another encoding the N-terminal domain of NMHC II-B fused to the C-terminal domain of II-A (Aba/Aba mice). 4-For control mice we inserted cDNA encoding NMHC II-A into the II-A locus. Replacing NM II-A with II-B (Ab*/Ab*) allows normal development of the visceral endoderm, gastrulation, organogenesis and survival to E9-10. These mice show a delay in embryonic turning with defects in the vasculature and endocardium. Aba/Aba mice die at the same age as Ab*/Ab* mice indicating that the N-terminal motor domains are interchangeable between II-A and II-B up to E9-10 despite differences in the kinetic properties of the motors. Aab/Aab mice survive beyond E12 with a normal vasculature but with a hypoplastic heart and an aorta overriding a ventricular septal defect. Thus, the N-terminal II-A motor domain has extended the developmental period from E9-10 to E13, displaying its importance for the early embryonic development.
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