C57BL/6N-Agtr1a^tm1Uky/J

Stock number: 016211
Research areas: Cardiovascular Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These AT1a^flox floxed mutant mice possess a loxP site upstream of exon 3 followed by a neomycin resistance (neo) cassette flanked by frt sites and loxP sites downstream of exon 3 of the Agtr1a gene. This strain may be useful for studying the role of cell specific Agtr1a expression on ascending aortic aneurysms.

Detailed description

These AT1a^flox mutant mice possess a loxP site upstream of exon 3 followed by a neomycin resistance (neo) cassette flanked by frt sites and loxP sites downstream of exon 3 of the angiotensin II receptor, type 1a (Agtr1a) gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. AGTR1A is expressed in vascular cells such as endothelial cells, smooth muscle cells, and macrophages. Angiotensin II (Ang II) is a vasoconstrictor which, upon binding to AGTR1A, can induce aneurysms in the ascending aorta. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 3 deleted in the cre-expressing tissues. When this floxed strain is crossed to a strain expressing Cre recombinase in smooth muscle, deletion of Agtr1a had no affect on ascending aortic aneurysms (AA) after Ang II infusion. In contrast, when crossed to a strain expressing Cre recombinase in endothelial cells, deletion of Agtr1a resulted in a reduction in ascending AA after Ang II infusion. This strain may be useful for studying the role of cell specific Agtr1a expression on ascending AA.

Development

A targeting vector was designed to insert a loxP site upstream of exon 3 followed by a neomycin resistance (neo) cassette flanked by frt sites and loxP sites downstream of exon 3 of the angiotensin II receptor, type 1a (Agtr1a) gene. The construct was electroporated into C57BL/6N-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the donating investigator reported that the resulting chimeric mice were bred to C57BL/6N mice (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the colony.

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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 4 of 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/6J ; C57BL/6N genetic background.

Allele

Symbol: Agtr1a^tm1Uky
Name: targeted mutation 1, Katherine Adams
MGI accession ID: MGI:4946096
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Agtr1a
Marker name: angiotensin II receptor, type 1a
Chromosome: 13
Strain of origin: C57BL/6N
Molecular note: A targeting vector was designed to insert a loxP site upstream of exon 3 followed by a neomycin resistance (neo) cassette flanked by frt sites and loxP sites downstream of exon 3 of the angiotensin II receptor, type 1a (Agtr1a) gene.