In order to study the function of the nonmuscle myosin II isoforms (NMII-A, II-B, and II-C), homologous recombination has been used to delete each isoform in embryonic stem cells and null mice have been generated. Deletion of nonmuscle myosin heavy chain (NMHC) II-A causes lethality prior to gastrulation (E6.5) and the embryos are disorganized with defects in cell-cell adhesion and a failure to form a columnar visceral endoderm. In order to avoid the early embryonic lethality, a nonmuscle myosin heavy chain (NMHC) II-A floxed mouse has been created. A neomycin-resistance cassette has been inserted into the intron 3 of exon 3 and loxP sites have been inserted flanking both the neomycin cassette and the exon. Matings of these mice to mice bearing cre recombinase under the control of a cell or tissue specific promoters causes the corresponding deletion of NM II-A. NMII-A is not expressed in mature cardiomyocytes but there is transient expression of NMII-A in the heart during early stages of development. In order to determine if NMII-A is necessary in cardiac precursors, NMII-A flox mice were crossed to mice bearing cre recombinase under control of the early cardiac marker, Nkx2.5. NMII-A was deleted and hearts were determined to be normal in size and morphology. However, the mice which were homozygous for the deletion (ANkx/ANkx) were undersized and died between 2-9 months of age. Since Nkx2.5 is also expressed in the spleen, stomach and tongue, these organs were sectioned and their morphology characterized. Lethality was determined to be due to development of squamous cell carcinoma of the tongue.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Heart, Lung, and Blood Institute
Zip Code
Baird, Michelle A; Billington, Neil; Wang, Aibing et al. (2017) Local pulsatile contractions are an intrinsic property of the myosin 2A motor in the cortical cytoskeleton of adherent cells. Mol Biol Cell 28:240-251
Naydenov, Nayden G; Feygin, Alex; Wang, Dongdong et al. (2016) Nonmuscle Myosin IIA Regulates Intestinal Epithelial Barrier in vivo and Plays a Protective Role During Experimental Colitis. Sci Rep 6:24161
Conti, Mary Anne; Saleh, Anthony D; Brinster, Lauren R et al. (2015) Conditional deletion of nonmuscle myosin II-A in mouse tongue epithelium results in squamous cell carcinoma. Sci Rep 5:14068
Recuenco, Mariam C; Ohmori, Tomoko; Tanigawa, Shunsuke et al. (2015) Nonmuscle Myosin II Regulates the Morphogenesis of Metanephric Mesenchyme-Derived Immature Nephrons. J Am Soc Nephrol 26:1081-91
Kwan, Raymond; Chen, Lu; Looi, Koksun et al. (2015) PKC412 normalizes mutation-related keratin filament disruption and hepatic injury in mice by promoting keratin-myosin binding. Hepatology 62:1858-69
Chandrasekar, Indra; Goeckeler, Zoe M; Turney, Stephen G et al. (2014) Nonmuscle myosin II is a critical regulator of clathrin-mediated endocytosis. Traffic 15:418-32
Ebrahim, Seham; Fujita, Tomoki; Millis, Bryan A et al. (2013) NMII forms a contractile transcellular sarcomeric network to regulate apical cell junctions and tissue geometry. Curr Biol 23:731-6
Crish, James; Conti, Mary Anne; Sakai, Takao et al. (2013) Keratin 5-Cre-driven excision of nonmuscle myosin IIA in early embryo trophectoderm leads to placenta defects and embryonic lethality. Dev Biol 382:136-48
Doyle, Andrew D; Kutys, Matthew L; Conti, Mary Anne et al. (2012) Micro-environmental control of cell migration--myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics. J Cell Sci 125:2244-56
Zhang, Yingfan; Conti, Mary Anne; Malide, Daniela et al. (2012) Mouse models of MYH9-related disease: mutations in nonmuscle myosin II-A. Blood 119:238-50

Showing the most recent 10 out of 23 publications