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
21
Fiscal Year
2011
Total Cost
$449,081
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
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