These C57BLKS.eNOS- mice are a C57BLKS-congenic strain with a knockout mutation of the nitric oxide synthase 3 endothelial cell gene (Nos3 or eNOS). They may be useful in studying albuminuria/diabetic nephropathy, insulin resistance, hyperlipidemia, hypertension and other cardiovascular defects, wound healing, and lung development.
IMR Colony, The Jackson Laboratory
These C57BLKS/J-congenic mice harbor a knockout mutation of the Nos3 gene. Homozygous mice (C57BLKS.eNOS-/-) are viable and fertile. C57BLKS.eNOS-/- mice develop moderate albuminuria (by 26 weeks of age) and moderate systemic hypertension (by 24-26 weeks of age).
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the C57BLKS.eNOS-/- strain. It should be noted that the C57BLKS.eNOS-/- phenotype could vary from that originally described for eNOS-/- mice on a C57BL/6-congenic background (described below). We may modify the C57BLKS.eNOS-/- strain description if necessary as published results become available.
When maintained on a C57BL/6-congenic background, eNOS-/- mice exhibit elevated blood pressure that is about 20 mmHg higher than that seen in normal wildtype siblings. They also show a decreased heart rate. Female homozygotes are smaller in body weight than normal wildtype siblings. Hyperglycemic-euglycemic clamp studies demonstrate that homozygotes exhibit insulin resistance at the level of the liver and peripheral tissues.
These C57BLKS.eNOS- mutant mice were generated by breeding males from the eNOS- C57BLKS/J Leprdb double mutant colony (Stock No. 008340) with C57BLKS/J inbred females (Stock No. 000662). The resulting offspring retaining the eNOS- mutation and wildtype at the Lepr locus were bred together to establish this C57BLKS.eNOS- colony as Stock No. 018295.
The eNOS knockout mutation was created by Dr. Oliver Smithies (University of North Carolina) as described for Stock No. 002684). It has a neomycin resistance cassette replacing 129 bp of exon 12 - this disrupted the calmodulin binding site of the protein and introduced a premature stop codon into the transcripts.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. One marker on Chromosome 5 was still segregating with the targeted mutation. Two markers on Chromosome 11 were found to still be segregating with C57BL/6J as in parental line Stock No. 008340.
|Allele Name||targeted mutation 1, University of North Carolina|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||ecNOS-; eNOS-; eNOSKO; NOS3-|
|Gene Symbol and Name||Nos3, nitric oxide synthase 3, endothelial cell|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A 1.2 kb neomycin cassette replaced 129 bp of exon 12 of the gene. This disrupted the calmodulin binding site of the protein and introduced a premature stop codon into the transcripts. Immunohistochemisty of heart and kidney sections from homozygous mutant mice confirmed that no detectable encoded protein was present.|
|Mutations Made By|| |
Dr. Oliver Smithies, University of North Carolina at Chapel Hill
When maintaining a live colony, mice homozygous for the Nos3 targeted mutation (eNOS-/-) may be bred together.
When using the eNOS- mouse strain in a publication, please cite the originating article(s) and include JAX stock #018295 in your Materials and Methods section.
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