B6.129S6(FVB)-Ptgs2^tm1.1Fun/J

Stock number: 008101
Product name: Ptgs2^Y385F
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research, Reproductive Biology Research

Description

These mutant mice have an amino acid substitution that inactivates the cyclooxygenase activity but not the peroxidase activity of the gene product. Mutant mice exhibit abnormal kidney development and function as well as elevated systolic blood pressure, which may make them useful in studies of thrombogenesis and hypertension.

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 are not fertile. The protein gene product does not have cyclooxygenase activity while the peroxidase activity is normal as measured by LPS induction of macrophages derived from mutant mice. Mutant mice are more sensitive to collagen treatment resulting in reduction of platelet numbers (indicating enhanced thrombogenesis) and exhibit a higher frequency of sudden death due to thromboxane receptor agonist treatment. No prolonged bleeding time from LPS administration is observed. Prostaglandin E metabolite levels are diminished in urine. Three month old mutant mice have elevated systolic blood pressure (measured by the tail cuff method). Homozygotes exhibit undersize, pale kidneys with atrophic cortices, interstitial inflammation, hypoplastic glomeruli and glomerulosclerosis. This mutant mouse strain may be useful in studies of thrombogenesis and hypertension.

Development

A targeting vector containing a loxP site flanked neomycin resistance gene and a point mutation was used to insert a Y385F substitution into exon 8. The construct was electroporated into 129S6/SvEvTac derived TL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The mice were crossed to the Cre recombinase expressing strain FVB/N-Tg(EIIa-cre)C5379Lmgd/J (Stock No. 003314) for two generations to remove the neo selection cassette, and then backcrossed to C57BL/6 for 10 generations.

Allele

Symbol: Ptgs2^tm1.1Fun
Name: targeted mutation 1.1, Colin D Funk
MGI accession ID: MGI:3629677
Generation method: Targeted
Marker symbol: Ptgs2
Marker name: prostaglandin-endoperoxide synthase 2
Chromosome: 1
Strain of origin: 129S6/SvEvTac
Molecular note: This allele was generated by Cre mediated recombination of Ptgs2^tm1Fun, resulting in the loss of the neomycin selection cassette.