B6.129(FVB)-Ptgs2^{tm2.1(Ptgs1)Fun}/J

Stock number: 008104
Research areas: Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Reproductive Biology Research

Description

COX-1>COX-2 knock-in/knock-out mice express Ptgs1 from the endogenous Ptgs2 locus, and develop chronic peritonitis and progressive kidney deterioration. COX1 protein (Ptgs1 gene product) is increased 5 fold in LPS-stimulated macrophages from homozygotes. This mutant mouse strain may be useful in studies of prostaglandin synthesis and inflammation.

Detailed description

Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. Female homozygotes have a longer period between successive pregnancies and reduced litter sizes. Ptgs1 gene product (protein), COX1, is increased approximately 5 fold in LPS-stimulated macrophages from homozygotes. Prostacyclin metabolite level in urine is reduced by 55% when compared to wildtype controls. No increase in prostaglandin-glycerol in mutant macrophages after LPS challenge is observed. Homozygotes exhibit reduced bradykinin-induced vasculature permeability and at 6 months of age have enlarged glomeruli due to increased inflammatory infiltrate. By 5 months of age, mutant mice develop chronic peritonitis and progressive renal cortex deterioration.

This mutant mouse strain may be useful in studies of prostaglandin synthesis and inflammation.

Development

A targeting vector containing the Ptgs2 promoter region, Ptgs1 coding region downstream of a loxP site flanked (floxed) PGK-neo selection cassette and exon 10 with a 3'-UTR region of Ptgs2 was used to disrupt most of coding region, including exons 1 to 10, of the endogenous Ptgs2 gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. The resulting chimeric animals were crossed to the Cre recombinase expressing strain FVB/N-Tg(EIIa-cre)C5379Lmgd/J (Stock No. 003314) to remove the neo selection cassette. The mice were then backcrossed to C57BL/6 for 5 generations.

Allele

Symbol: Ptgs2^{tm2.1(Ptgs1)Fun}
Name: targeted mutation 2.1, Colin D Funk
MGI accession ID: MGI:3699107
Generation method: Targeted
Attributes: Null/Knockout; Inserted expressed sequence
Marker symbol: Ptgs2
Marker name: prostaglandin-endoperoxide synthase 2
Chromosome: 1
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Expressed genes: Ptgs1,prostaglandin-endoperoxide synthase 1,mouse, laboratory
Molecular note: A floxed neo was removed from the locus, leaving cDNA encoding encoding prostaglandin-endoperoxide synthase 1 to replace most of the coding region of the endogenous locus (exons 1-9).