STOCK Arg2^tm1.1Frsv/J

Stock number: 036077
Product name: Arg2^lox
Research areas: Developmental Biology Research, Endocrine Deficiency Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

Arg2^lox mice have loxP sites flanking exons 3-6 of the Arg2 gene. This strain is useful for studying the formation of the corticomedullary urea gradient and attenuation of kidney damage during ischemia-reperfusion injury.

Detailed description

Arg2^lox mice have loxP sites flanking exons 3-6 of the arginase type II (Arg2) gene. Arg2 encodes a mitochondrial enzyme which catalyzes the hydrolysis of arginine to ornithine and urea. The type II isoform encoded by this gene is expressed in extra-hepatic tissues, especially kidney. It has been shown to play a role in cancer, asthma, cardiovascular disease, diabetes and retinal degeneration, and is upregulated in a variety of renal pathologies, including ischemia-reperfusion (IR) injury. Homozygous mice are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 3-6 deleted in Cre-expressing tissues.

When bred to Pax8-rtTa/LC1 double transgenic mice (Pax8-rtTA [Stock No. 007176] and LC1 [Tg(tetO-cre)LC1Bjd]) with Tet-inducible expression of Cre recombinase in renal tubular epithelial cells, the resulting Arg2^lox/lox/Pax8-rtTa/LC1 offspring (cKO) have Arg2 exons 3-6 removed after 2 week administration of doxycycline. Those cKO mice exhibit impaired urea concentration and osmolality gradients along the corticomedullary axis. In a model of unilateral ischemia-reperfusion injury (UIRI) cKO mice exhibit a broad range of renal functional abnormalities, including albuminuria and aminoaciduria compare to WT mice.

Development

The Arg2^lox targeting vector was designed to insert a loxP site upstream of exon 3 and frt-flanked neomycin resistance (neo) cassette, in reverse orientation to the gene, downstream of exon 6 of the arginase type II (Arg2) gene. A second loxP site was inserted downstream of the neo cassette. The construct was electroporated into C57BL/6 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred with C57BL/6J mice (Stock No. 000664). Resulting offspring were bred to FLP-expressing mice, on a C57BL/6 genetic background, to remove the neo cassette. Progeny were crossed to remove the FLP-expressing transgene. Resulting Arg2^lox mice were maintained on a C57BL/6 genetic background prior to arrival at The Jackson Laboratory (see SNP note below). Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.



In 2021, 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 43 markers throughout the genome were segregating with an unknown source. Also, 4 of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating, including the rd8 recessive mutation associated with retinal degeneration on Chromosome 1 within the Crb1 locus. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.

Allele

Symbol: Arg2^tm1.1Frsv
Name: targeted mutation1.1, Dmitri Firsov
MGI accession ID: MGI:6505264
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Arg2^lox
Marker symbol: Arg2
Marker name: arginase type II
Marker synonyms: AII
Chromosome: 12
Strain of origin: C57BL/6
Molecular note: The targeting vector is designed to insert a loxP site upstream of exon 3 and an FRT-flanked neomycin resistance (neo) cassette, in reverse orientation to the gene, downstream of exon 6. A second loxP site is inserted downstream of the neo cassette. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exons 3 through 6 floxed.