Description

Strain Information

Former Names B6.129S6-Ptgs2tm1.1Fun/J    (Changed: 30-NOV-07 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Heterozygote x Homozygote         (Female x Male)   27-APR-10 Species laboratory mouse Generation N11+F9 (30-JUN-11) Generation Definitions   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 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.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ptgs2

008104	B6.129(FVB)-Ptgs2tm2.1(Ptgs1)Fun/J
002476	B6;129S-Ptgs2tm1Jed/J
017551	B6;D2-Tg(Nphs1-Ptgs2)14Rhrs/J

View Strains carrying other alleles of Ptgs2     (3 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Ptgs2^tm1.1Fun/Ptgs2^tm1.1Fun

        involves: 129S6/SvEvTac * C57BL/6

• renal/urinary system phenotype
• abnormal kidney cortex morphology
  • atrophic   (MGI Ref ID J:109548)
• • abnormal renal glomerulus morphology
    • hypoplastic   (MGI Ref ID J:109548)
  • • glomerulosclerosis
      • moderate   (MGI Ref ID J:109548)
• pale kidney   (MGI Ref ID J:109548)
• small kidney   (MGI Ref ID J:109548)
• reproductive system phenotype
• reduced female fertility
  • number of term pregnancies reduced   (MGI Ref ID J:109548)
• homeostasis/metabolism phenotype
• decreased prostaglandin level
  • near absence of LPS induced synthesis   (MGI Ref ID J:109548)

Ptgs2^tm1.1Fun/Ptgs2^tm1.1Fun

        involves: 129S6/SvEvTac

• renal/urinary system phenotype
• abnormal kidney cortex morphology
  • almost complete loss of the cortical mantle   (MGI Ref ID J:148699)
  • display atrophic cortices   (MGI Ref ID J:148699)
• • decreased renal glomerulus number
    • hypoplastic glomeruli   (MGI Ref ID J:148699)
  • glomerulosclerosis
    • mild to moderate   (MGI Ref ID J:148699)
• kidney inflammation
  • moderate interstitial inflammation   (MGI Ref ID J:148699)
• homeostasis/metabolism phenotype
• increased blood urea nitrogen level   (MGI Ref ID J:148699)
• immune system phenotype
• kidney inflammation
  • moderate interstitial inflammation   (MGI Ref ID J:148699)

View Research Applications

Research Applications

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

Cardiovascular Research
Hypertension
Vascular Defects
      Thrombosis

Developmental Biology Research
Internal/Organ Defects
      kidney

Internal/Organ Research
Kidney Defects

Reproductive Biology Research
Fertility Defects
      females only

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ptgs2tm1.1Fun
Allele Name		targeted mutation 1.1, Colin D Funk
Allele Type		Targeted (knock-in)
Common Name(s)		Ptgs2Y385F; Y371F;
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TL1/TL-1
ES Cell Line Strain		129S6/SvEvTac
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		This allele was generated by Cre mediated recombination of Ptgs2tm1Fun, resulting in the loss of the neomycin selection cassette. [MGI Ref ID J:109548]

Genotyping

Genotyping Information

Genotyping Protocols

Ptgs2^tm1.1Fun, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Yu Y; Fan J; Chen XS; Wang D; Klein-Szanto AJ; Campbell RL; Fitzgerald GA; Funk CD. 2006. Genetic model of selective COX2 inhibition reveals novel heterodimer signaling. Nat Med 12(6):699-704. [PubMed: 16732282]  [MGI Ref ID J:109548]

Additional References

Ptgs2^tm1.1Fun related

Li W; Wu S; Ahmad M; Jiang J; Liu H; Nagayama T; Rose ME; Tyurin VA; Tyurina YY; Borisenko GG; Belikova N; Chen J; Kagan VE; Graham SH. 2010. The cyclooxygenase site, but not the peroxidase site of cyclooxygenase-2 is required for neurotoxicity in hypoxic and ischemic injury. J Neurochem 113(4):965-77. [PubMed: 20236388]  [MGI Ref ID J:160224]

Seta F; Chung AD; Turner PV; Mewburn JD; Yu Y; Funk CD. 2009. Renal and cardiovascular characterization of COX-2 knockdown mice. Am J Physiol Regul Integr Comp Physiol 296(6):R1751-60. [PubMed: 19357295]  [MGI Ref ID J:148699]

Zhang H; Ching S; Chen Q; Li Q; An Y; Quan N. 2008. Localized inflammation in peripheral tissue signals the CNS for sickness response in the absence of interleukin-1 and cyclooxygenase-2 in the blood and brain. Neuroscience 157(4):895-907. [PubMed: 18950689]  [MGI Ref ID J:144882]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	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.
Mating System	Heterozygote x Homozygote         (Female x Male)   27-APR-10
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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