B6;129S4-Ptgs2^tm1Hahe/J

Stock number: 030785
Product name: Cox-2^flox
Research areas: Cardiovascular Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Cox-2^flox mice possess loxP sites flanking exons 4-5 of the prostaglandin-endoperoxide synthase 2 (Ptgs2) gene making them useful for studying pain, inflammation, and cancer progression.

Detailed description

Cox-2^flox mice possess loxP sites flanking exons 4-5 of the prostaglandin-endoperoxide synthase 2 (Ptgs2) gene. Ptgs2 encodes Cyclooxygenase-2 (Cox-2), an enzyme that catalyzes the conversion of arachidonic acid to Prostaglandin H (PGH), and eventually to prostanoid lipids. Cox-2 plays a role in thermoregulation, pain perception, inflammation, cardiovascular function, cancer, and neurodegenerative diseases and is a drug target for Cox-2-inhibitors such as non-steroidal anti-inflammatory drugs (NSAIDs). Cox-2 has also been associated with UV-induced tumor development and progression. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 4-5 deleted in cre-expressing tissues.

When bred to B6.129P2-Lyz2^tm1(cre)Ifo/J mice (Stock No. 004781) expressing Cre recombinase in myeloid cells, these mice exhibit weight loss, increased clinical scores, and decreased epithelial cell proliferation after colitis was induced with dextran sulfate sodium (DSS).

Development

The Cox-2^flox targeting vector was designed to insert a single loxP site upstream of exon 4 and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 5 of the prostaglandin-endoperoxide synthase 2 (Ptgs2) gene. The construct was electroporated into 129S4/SvJae-derived LW1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with the pTURBO-Cre expression plasmid to delete the neo cassette. Resulting ES cells contained multiple gene rearrangments; intact floxed-exons 4-5, intact floxed-neo cassette, or excision of both exons 4-5 and the neo cassette. Correctly targeted ES cells, containing only the Cox-2^flox allele, were injected into C57BL/6 blastocysts and resulting chimeric males were bred with C57BL/6 females. Resulting offspring were maintained on a mixed genetic background. 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/6J oocytes (Stock No. 000664).

Allele

Symbol: Ptgs2^tm1Hahe
Name: targeted mutation 1, Harvey R Herschman
MGI accession ID: MGI:3623499
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Cox-2^flox; Ptgs2^tm1Hrh
Marker symbol: Ptgs2
Marker name: prostaglandin-endoperoxide synthase 2
Marker synonyms: COX2; COX-2; cyclooxygenase 2; cyclooxygenase-2; GRIPGHS; hCox-2; PGG/HS; Pghs2; PGHS-2; PHS II; PHS-2; prostaglandin G/H synthase; Tis10
Chromosome: 1
Strain of origin: 129S4/SvJae
Molecular note: A targeting vector was designed to flank exons 4 and 5 with loxP sites. Deletion of these exons would cause a frame shift, resulting in a stop codon after eight missense amino acids in exon 6.