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.
Colin D. Funk, Queen's University
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted | Ptgs2 | prostaglandin-endoperoxide synthase 2 |
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.
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 Name | targeted mutation 1.1, Colin D Funk |
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Allele Type | Targeted |
Allele Synonym(s) | (COX)-2-; Ptgs2Y385F; Y371F |
Gene Symbol and Name | Ptgs2, prostaglandin-endoperoxide synthase 2 |
Gene Synonym(s) | |
Promoter | Ptgs2, prostaglandin-endoperoxide synthase 2, mouse, laboratory |
Strain of Origin | 129S6/SvEvTac |
Chromosome | 1 |
Molecular Note | This allele was generated by Cre mediated recombination of Ptgs2tm1Fun, resulting in the loss of the neomycin selection cassette. |
When maintaining a live colony of these mice, heterozygotes may be interbred or heterozygous females may be crossed with homozygous males. Homozygous females are not fertile.
When using the Ptgs2Y385F mouse strain in a publication, please cite the originating article(s) and include JAX stock #008101 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Ptgs2<tm1.1Fun> |
Frozen Mouse Embryo | B6.129S6(FVB)-Ptgs2<tm1.1Fun>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129S6(FVB)-Ptgs2<tm1.1Fun>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129S6(FVB)-Ptgs2<tm1.1Fun>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129S6(FVB)-Ptgs2<tm1.1Fun>/J Frozen Embryo | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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