Generation of a conditional allele for the mouse endothelial nitric oxide synthase gene

Genesis. 2012 Sep;50(9):685-92. doi: 10.1002/dvg.22026. Epub 2012 May 10.

Abstract

Mice with endothelial nitric oxide synthase (eNOS) deletions have defined the crucial role of eNOS in vascular development, homeostasis, and pathology. However, cell specific eNOS function has not been determined, although an important role of eNOS has been suggested in multiple cell types. Here, we have generated a floxed eNOS allele in which exons 9-12, encoding the sites essential to eNOS activity, are flanked with loxP sites. Mice homozygous for the floxed allele showed normal eNOS protein levels and no overt phenotype. Conversely, homozygous mice with Cre-deleted alleles displayed truncated eNOS protein, lack of vascular NO production, and exhibited similar phenotype to eNOS knockout mice, including hypertension, low heart rate, and focal renal scarring. These findings demonstrate that the floxed allele is normal and it can be converted to a non-functional eNOS allele through Cre recombination. This mouse will allow time- and cell-specific eNOS deletion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles*
  • Animals
  • Blood Pressure / genetics
  • Embryonic Stem Cells
  • Endothelium / enzymology
  • Exons
  • Female
  • Gene Deletion
  • Gene Targeting
  • Genetic Engineering / methods*
  • Heart Rate / genetics
  • Homozygote
  • Hypertension / genetics
  • Integrases
  • Kidney / pathology
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / genetics*
  • Nitric Oxide Synthase Type III / metabolism
  • Phenotype
  • Recombination, Genetic

Substances

  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Cre recombinase
  • Integrases