B6(SJL)-Noxa1^tm1.1Mrng/J

Stock number: 039418
Product name: Noxa1^-
Research areas: Cardiovascular Research, Developmental Biology Research, Research Tools

Description

Noxa1^-/- knock-out mice lack the entire coding region of the Noxa1 gene. These mice may be useful for studying the role of NADPH oxidase in vascular remodeling and atherogenesis.

Detailed description

Noxa1^-/- knock-out mice lack the entire coding region of the NADPH oxidase activator 1 (Noxa1) gene. Noxa1 encodes a protein that activates NADPH oxidases which regulate superoxide production in vascular tissues. In vascular smooth muscle cells (VSMC), NOXA1 interacts with p47phox and is critical component of NOX1 NADPH oxidase where it influences vasoconstriction, hypertension, and cellular and neuronal growth and apoptosis. Nox1 expression is induced in neointimal SMC after vascular injury where it mediates cell migration, proliferation, and extracellular matrix production; while Nox1 deletion significantly reduces neointima hyperplasia. Expression of NOXA1 is increased in aortas of Apoe^-/- mice and in early stages of atherosclerosis in human carotid arteries.

Homozygous Noxa1^-/- knock-out mice are viable and fertile with no overt phenotype. They were similar to wildtype mice in body weight, plasma cholesterol, and triglycerides levels after 12 weeks of Western diet. Immunohistochemical staining shows no expression of NOXA1 in aorta medial layer of Noxa1^-/- mice. Mice show minimal or complete absence of neointima hyperplasia after femoral artery guide wire injury compared to wildtype mice, with no change in NOX1 expression.

When Noxa1^-/- mice were crossed with Apoe^-/- mice (Stock No. 002052) and fed a Western diet, resulting Noxa1^-/-/Apoe^-/- mice show a protective cardiovascular phenotype, with reduced atherosclerotic lesion size and lower reactive oxygen species (ROS) levels.

Noxa1^-/- mice are also found to be protected against Ang II-induced hypertension.

Development

These Noxa1^-/- knock-out mice were made by replacing the entire coding region of the NADPH oxidase activator 1 (Noxa1) gene with a neomycin resistance (neo) cassette flanked by loxP and frt sites. The construct was electroporated into C57BL/6NTac-derived IC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c blastocysts and the chimeric mice were bred to C57BL/6J mice (Stock No. 000664). Offspring were bred with ACTB:FLPe mice (Stock No. 005703) to remove the neo cassette and resulting offspring were bred to C57BL/6J mice to remove the FLPe-expressing transgene. The resulting Noxa1^-/- mice were further bred to C57BL/6J mice for at least 10 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.



A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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 males sent to The Jackson Laboratory Repository. Two of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Noxa1^tm1.1Mrng
Name: targeted mutation 1, Marschall S Runge
MGI accession ID: MGI:7621673
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Noxa1^-
Marker symbol: Noxa1
Marker name: NADPH oxidase activator 1
Marker synonyms: NY-CO-31; p51NOX; SDCCAG31
Chromosome: 2
Strain of origin: C57BL/6NTac
Molecular note: The entire coding region spaning 12 exaons of the NADPH oxidase activator 1 (Noxa1) gene was replaced with a neomycin resistance (neo) cassette flanked by loxP and frt sites by targeted homologous recombination in ES cells. The neo cassette was removed by crossing with FLPe expressing mice.