FVB.129P2(Cg)-Itgav^tm2Hyn/J

Stock number: 032298
Product name: αv^flox
Research areas: Neurobiology Research, Research Tools

Description

Exon 4 of the mouse Itgav gene is flanked by loxP sites in these αv^flox mice. Cre-mediated excision of the floxed region results in a knock-out allele useful in studies of ulcerative colitis, autoimmunity, vascular development, and cancer.

Detailed description

αv integrins are major endothelial fibronectin receptors that play key roles in the regulation of mucosal immunity, vascular development, and cancer.

Exon 4 of the mouse Itgav (integrin alpha V) gene is flanked by loxP sites in this αv^flox targeted mutant strain. Cre-mediated excision of the floxed region results in a knock-out allele. Homozygous floxed mice are viable, fertile, and without overt phenotype. This FVB genetic background line was developed for use in MMTVPyMT mammary tumor line mice (see Stock No. 002374).

When mixed background animals (129, C57BL/6, FVB) are crossed with mice expressing the Tek-cre (Tie2-cre) allele (see Stock No. 008863) in endothelial cells and hemangioblasts/hematopoietic cells, pups are born at expected frequencies. But from 12 weeks of age onward, they begin to lose weight, body condition, and die prematurely. Death is attributed to a constriction of the intestine. Inflammation is seen in the colon and cecum from 14 weeks onward, with infiltrates of lymphocytes, monocytes, and plasma cells. Inflammation is chronic and progressive, leading to ulcers, acute inflammatory infiltrates, and crypt abscesses by 20 weeks and extensive epithelial proliferation, regeneration, and adenocarcinoma from 40 weeks onward. Inflammation is also found in the peritoneum, in the liver, and, in approximately 40% of mice, in the nasal cavity and respiratory tract.

Crosses of the same αv^flox mice with Tek-cre animals have no effect on developmental angiogenesis. However, the combined absence of endothelial Itga5 (see floxed Stock No. 032298) and Itgav causes extensive defects in remodeling of the great vessels and heart resulting in death at approximately embryonic day 14.5 (E14.5).

This allele has been crossed with a number of Cre recombinase-expressing lines, particularly those associated with vascular and hematopoietic specificities. Among these strains: Tek-cre (Tie2-cre; see Stock No. 008863), LysM-cre (Lyz2-cre; see Stock No. 004781), Nes-cre (see Stock No. 003771), Cd4-cre (see Stock No. 022071), Cd19-cre (see Stock No. 006785), Wnt1-cre (a component of Stock No. 009107), Tagln-cre (SM22-cre; see Stock No. 017491), and Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj} (see Stock No. 008463). This floxed strain has been found to delete well with all Cre recombinase lines tested.

Development

A loxP-flanked neomycin cassette (in reverse orientation) was inserted at an XbaI site 5' of the start of exon 4, and an additional loxP site was placed 3' of exon 4. The mutation was created via homologous recombination in 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. The neomycin cassette was removed from the ES cells via transient transfection with Cre recombinase. Minimal crosses to other 129- and C57BL/6-background strains were used during the management of this line, but are said to no longer make a significant contribution to the genetic background of this line. This strain was bred to FVB/NJ for many generations by the donating laboratory.

Allele

Symbol: Itgav^tm2Hyn
Name: targeted mutation 2, Richard Hynes
MGI accession ID: MGI:3759836
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: alphav^flox
Marker symbol: Itgav
Marker name: integrin alpha V
Marker synonyms: 1110004F14Rik; 2610028E01Rik; alphav-integrin; CD51; D430040G12Rik; IDNDC; MSK8; vitronectin receptor alpha polypeptide (VNRA); VNRA; VTNR
Chromosome: 2
Strain of origin: 129P2/OlaHsd
Molecular note: A floxed neo cassette was inserted at the 5' start of exon 4 and additional loxP site was inserted downstream of exon 4 to create a floxed allele. The neo cassette was removed by cre-mediated recombination (source not specified). Insertion was confirmed by PCR and Southern blot.