B6(SJL)-Rras^tm1.1Masak/J

Stock number: 036202
Product name: Rras^fl
Research areas: Cardiovascular Research, Developmental Biology Research, Research Tools

Description

Rras^fl/fl mice have loxP sites flanking exons 2-6 of the Rras gene. This strain is useful for studying vascular development and homeostasis.

Detailed description

Rras^fl/fl mice have loxP sites flanking exons 2-6 of the RAS related (Rras) gene. Rras encodes a small GTPase abundantly expressed in smooth muscle cells of various organs as well as endothelial cells and pericytes of mature blood vessels. It is also expressed at lower levels in fibroblasts, neurons, and some immune cells.

R-ras has been shown to regulate angiogenesis, vascular homeostasis and regeneration, cell adhesion, neuronal axon guidance, and adaptive immunity. R-RAS is down-regulated in the hyperplastic arterial smooth muscle, angiogenic blood vessels, and in the dysfunctional vasculature in diabetic retinopathy and cancers. Homozygous mice are viable and fertile.

When bred to Pdgfrb-cre mice, resulting pericyte-conditional KO mice (PC-cKO) exhibit perturbed retinal vascular development with excessive endothelial cell proliferation, sprouting, and branching of capillary plexus associated with diminished pericyte coverage and basement membrane. Furthermore, these mice frequently present microphthalmia at birth.

When bred to Cdh5-CreERT2 mice, resulting endothelial cell-conditional KO impairs the ability of high endothelial venules to recruit naive T cells to the lymph nodes upon acute inflammation after tamoxifen induction.

Development

The Rras^fl targeting vector was designed to insert a loxP sites flanking exons 2-6 of the RAS related (Rras) gene. A frt-flanked neomycin selection cassette was inserted downstream of exon 6. The construct was electroporated into iTL IC1-derived C57BL/6NTac embryonic stem (ES) cells. Resulting ES cells were injected into blastocysts and resulting chimeric mice were bred to to B6.Cg-Tg(ACTFLPe)9205Dym/J (Stock No. 005703) to remove the neo cassette. Progeny were crossed to remove the FLPe-expressing transgene, and offspring were further bred to C57BL/6NHsd mice for at least 5 generations by the donating laboratory (see SNP note below). Upon arrival at The Jackson Laboratory Repository, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).

Of note, this strain does not carry the C57BL/6NHsd-derived Dock2^m1Hsd spontaneous mutation.

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 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 C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Rras^tm1.1Masak
Name: targeted mutation 1.1, Masanobu Komatsu
MGI accession ID: MGI:6509163
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Rras^fl; Rras^tm2Itl
Marker symbol: Rras
Marker name: related RAS viral (r-ras) oncogene
Marker synonyms: p23; R-Ras; Rras1
Chromosome: 7
Strain of origin: C57BL/6NTac
Molecular note: The targeting vector contains a loxP site upstream of exon 2 and a second loxP site downstream of exon 6. An FRT-flanked neomycin selection cassette is inserted downstream of exon 6. Flp-mediated recombination removed the FRT-flanked neo cassette.