title: Generation of a conditional allele for the mouse endothelial nitric oxide synthase gene.
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.
authors.affiliation: Division of Nephrology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Rosie
authors.initials: R
authors.lastname: Jiang
authors.forename: Suwan
authors.initials: S
authors.lastname: Wang
authors.forename: Keiko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fujita
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Fruci
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Breyer
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Harris
authors.forename: Takamune
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000483:Alleles; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D053595:Embryonic Stem Cells; D004727:Endothelium / Q000201:enzymology; D005091:Exons; D005260:Female; D017353:Gene Deletion; D018390:Gene Targeting; D005818:Genetic Engineering / Q000379:methods*; D006339:Heart Rate / Q000235:genetics; D006720:Homozygote; D006973:Hypertension / Q000235:genetics; D019426:Integrases; D007668:Kidney / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011995:Recombination, Genetic
chemical_list: D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C045073:Cre recombinase; D019426:Integrases