Description

Strain Information

Former Names B6.129-Ptgs2tm2.1(Ptgs1)Fun/J    (Changed: 30-NOV-07 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N6+F1 (20-SEP-08)   Donating Investigator Colin Funk,   Queen's University

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.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ptgs2

008101	B6.129S6(FVB)-Ptgs2tm1.1Fun/J
002476	B6;129S-Ptgs2tm1Jed/J

View Strains carrying other alleles of Ptgs2     (2 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Ptgs2^{tm2.1(Ptgs1)Fun}/Ptgs2^{tm2.1(Ptgs1)Fun}

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB

• renal/urinary system phenotype
• abnormal renal glomerulus morphology (MGI Ref ID J:118171)
  • in older mice, glomeruli are enlarged to due increased glomerular cellularity
  • cross-sectional area is increased ~56% in mutants compared to wild-type
• abnormal urine chemistry (MGI Ref ID J:118171)
  • urinary prostanglandin biosynthesis (eg. prostacyclin production) is decreased by 55% relative to wild-type
• kidney inflammation (MGI Ref ID J:118171)
  • glomeruli have increase inflammatory cell infiltration
• homeostasis/metabolism phenotype
• abnormal urine chemistry (MGI Ref ID J:118171)
  • urinary prostanglandin biosynthesis (eg. prostacyclin production) is decreased by 55% relative to wild-type
• increased blood urea nitrogen level (MGI Ref ID J:118171)
  • BUN levels are increased ~2-fold vs wild-type at 6 months of age
• cardiovascular system phenotype
• decreased vascular permeability (MGI Ref ID J:118171)
  • dye extravasation in the ear vasculature is decreased by 50-60% with bradykinin challenge compared to wild-type
• immune system phenotype
• abnormal macrophage physiology (MGI Ref ID J:118171)
  • upon LPS stimulation and 20-30 uM arachadonic acid, induced mutant macrophages produce prostaglandin E2 similar to wild-type levels
  • upon LPS stimulation with endognenous or very low exogenous substrate, levels of PGE2 produced by mutant macrophages are much lower than wild-type
• kidney inflammation (MGI Ref ID J:118171)
  • glomeruli have increase inflammatory cell infiltration
• peritoneal inflammation (MGI Ref ID J:118171)
  • at 5 months of age, mice show chronic peritonitis
• digestive/alimentary phenotype
• peritoneal inflammation (MGI Ref ID J:118171)
  • at 5 months of age, mice show chronic peritonitis
• reproductive system phenotype
• abnormal fertility/fecundity (MGI Ref ID J:118171)
  • females show a longer period between successive pregnancies
• decreased litter size (MGI Ref ID J:118171)
  • litter size is somewhat reduced compared to wild-type

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Endocrine Deficiency Research
Kidney Defects

Immunology and Inflammation Research
Inflammation

Reproductive Biology Research
Endocrine Deficiencies Affecting Gonads

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ptgs2tm2.1(Ptgs1)Fun
Allele Name		targeted mutation 2.1, Colin D Funk
Allele Type		Targeted (knock-in)
Common Name(s)		COX-1 > COX-2;
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Ptgs2, prostaglandin-endoperoxide synthase 2
Chromosome		1
Gene Common Name(s)		COX-2; COX2; GRIPGHS; PGG/HS; PGHS-2; PHS-2; Pghs2; Tis10; cyclooxygenase 2; cyclooxygenase-2; hCox-2; prostaglandin G/H synthase;
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). [MGI Ref ID J:118171]

Genotyping

Genotyping Information

Genotyping Protocols

Ptgs2^{tm2.1(Ptgs1)Fun}, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Yu Y; Fan J; Hui Y; Rouzer CA; Marnett LJ; Klein-Szanto AJ; FitzGerald GA; Funk CD. 2007. Targeted cyclooxygenase gene (ptgs) exchange reveals discriminant isoform functionality. J Biol Chem 282(2):1498-506. [PubMed: 17110378]  [MGI Ref ID J:118171]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred by crossing heterozygous females to homozygous males. Female homozygotes have a longer period between successive pregnancies and reduced litter sizes.
Mating System	Heterozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

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.

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Terms of Use

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General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

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