129S6.129P2(B6)-Nos3^tm1Unc/J

Stock number: 008286
Product name: 129S6-Nos3
Research areas: Cardiovascular Research, Diabetes and Obesity Research, Internal/Organ Research, Metabolism Research

Description

129S6/SvEvTac mice homozygous for this Nos3 (nitric oxide synthase 3, endothelial cell) targeted mutation, Nos3^tm1Unc, provide another genetic background that may be useful for studying wound healing, hypertension and other cardiovascular defects, insulin resistance, hyperlipidemia and lung development.

Detailed description

Homozygous mutant mice 129S6/SvEvTac background are viable, fertile, normal in size and do not exhibit any gross physical or behavioral abnormalities.

On the C57BL/6 congenic background homozygous mutants 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. This mutant mouse strain may be useful in studies of wound healing, hypertension and other cardiovascular defects, insulin resistance, hyperlipidemia and lung development.

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 strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to replace 129bp exon 12, which disrupted the calmodulin binding domain. The construct was electroporated into 129P2OlaHsd derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting male chimeric animals were crossed to C57BL/6 female mice. Heterozygotes were intercrossed to generate homozygotes. The mice were subsequently backcrossed on to the C57BL/6J background for 12 generations. The mice were then backcrossed to 129S6/SvEvTac for at least 10 generations prior to intercrossing. In 2008, The Jackson Laboratory backcrossed this stock to 129S6/SvEvTac for one generation prior to intercrossing to generate homozygotes. Additional SNP's testing indicates 104 markers tested spanning all chromosomes are 129S6 in origin.

Allele

Symbol: Nos3^tm1Unc
Name: targeted mutation 1, University of North Carolina
MGI accession ID: MGI:1857229
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Nos3
Marker name: nitric oxide synthase 3, endothelial cell
Chromosome: 5
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.