Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N5F2pN1 (10-OCT-04)   Donating Investigator Richard Breyer,   Vanderbilt 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. Reduced fertility in homozygous females is due to a pre-implantation defect. Fewer eggs are released during ovulation, of which fewer are fertilized and implanted when compared to wildtype controls, resulting in smaller litters (3 pups/litter). Mutant mice display slightly elevated baseline systolic blood pressure. Prostaglandin 2 infusion or high salt diet causes systolic hypertension in homozygous mice. This mutant mouse strain represents a model that may be useful in studies of salt sensitive hypertension and infertility.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes driven by the mouse phosphoglycerate kinase promoter was used to disrupt sequence of the targeted gene encoding the N-terminal of the protein. The construct was electroporated into 129S6/SvEv derived TL-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were backcrossed to C57BL/6 females. Simple sequence length polymorphism (SSLP) analysis confirmed that there are no chromosomal segments derived from 129, except for regions immediately flanking the disrupted locus, proximal chromosome 14.

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.

Ptger2^tm1Brey/Ptger2^tm1Brey

        involves: 129S6/SvEvTac * C57BL/6

• lethality-prenatal/perinatal
• *normal* lethality-prenatal/perinatal (MGI Ref ID J:53646)
  • no increase in neonatal mortality
• cardiovascular system phenotype
• abnormal vasodilation (MGI Ref ID J:53646)
  • PGE2-dependent vasodilation effects lost
• increased blood pressure (MGI Ref ID J:53646)
  • 8-16 week old females with significantly increased systolic pressure
  • increased systolic pressure in males as well but not statistically significant
  • reversible increase in blood pressure when placed on a high salt diet
• reproductive system phenotype
• decreased litter size (MGI Ref ID J:53646)
  • litter sizes from crosses of homozygous males and females were reduced
• reduced female fertility (MGI Ref ID J:53646)
  • reduced number of implantations when assessed at E5
  • reduced ovulation and fertilization only about 50% regardless of male genotype

View Research Applications

Research Applications

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

Ptger2^tm1Brey related

Cardiovascular Research
Hypertension (diet-induced)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ptger2tm1Brey
Allele Name		targeted mutation 1, Richard M Breyer
Allele Type		Targeted (knock-out)
Common Name(s)		EP2-;
Mutation Made By		Richard Breyer,   Vanderbilt University
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		TL1/TL-1
ES Cell Line Strain		129S6/SvEvTac
Gene Symbol and Name		Ptger2, prostaglandin E receptor 2 (subtype EP2)
Chromosome		14
Gene Common Name(s)		EP2; EP2 receptor; Ptger-ep2; Ptgerep2; prostaglandin E receptor EP2 subtype;
Molecular Note		A PGK-neomycin resistance cassette replaced part of the amino terminal coding sequence, including 420 bp from the ATG start codon to codon 140. [MGI Ref ID J:53646]

Genotyping

Genotyping Information

Genotyping Protocols

Ptger2^tm1Brey, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Kennedy CR; Zhang Y; Brandon S; Guan Y; Coffee K; Funk CD; Magnuson MA; Oates JA; Breyer MD; Breyer RM. 1999. Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor. Nat Med 5(2):217-20. [PubMed: 9930871]  [MGI Ref ID J:53646]

Additional References

Ptger2^tm1Brey related

Breyer RM; Kennedy CR; Zhang Y; Guan Y; Breyer MD. 2002. Targeted gene disruption of the prostaglandin E2 EP2 receptor. Adv Exp Med Biol 507:321-6. [PubMed: 12664604]  [MGI Ref ID J:87823]

Brouxhon S; Konger RL; VanBuskirk J; Sheu TJ; Ryan J; Erdle B; Almudevar A; Breyer RM; Scott G; Pentland AP. 2007. Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness. J Invest Dermatol 127(2):439-46. [PubMed: 16977324]  [MGI Ref ID J:117581]

Brouxhon S; Kyrkanides S; O'Banion MK; Johnson R; Pearce DA; Centola GM; Miller JN; McGrath KH; Erdle B; Scott G; Schneider S; VanBuskirk J; Pentland AP. 2007. Sequential down-regulation of E-cadherin with squamous cell carcinoma progression: loss of E-cadherin via a prostaglandin E2-EP2 dependent posttranslational mechanism. Cancer Res 67(16):7654-64. [PubMed: 17699770]  [MGI Ref ID J:124339]

Chang SH; Ai Y; Breyer RM; Lane TF; Hla T. 2005. The prostaglandin E2 receptor EP2 is required for cyclooxygenase 2-mediated mammary hyperplasia. Cancer Res 65(11):4496-9. [PubMed: 15930264]  [MGI Ref ID J:98801]

Fortner CN; Breyer RM; Paul RJ. 2001. EP2 receptors mediate airway relaxation to substance P, ATP, and PGE2. Am J Physiol Lung Cell Mol Physiol 281(2):L469-74. [PubMed: 11435222]  [MGI Ref ID J:108642]

Imig JD; Breyer MD; Breyer RM. 2002. Contribution of prostaglandin EP(2) receptors to renal microvascular reactivity in mice. Am J Physiol Renal Physiol 283(3):F415-22. [PubMed: 12167591]  [MGI Ref ID J:78902]

Keith RL; Geraci MW; Nana-Sinkam SP; Breyer RM; Hudish TM; Meyer AM; Malkinson AM; Dwyer-Nield LD. 2006. Prostaglandin E2 receptor subtype 2 (EP2) null mice are protected against murine lung tumorigenesis. Anticancer Res 26(4B):2857-61. [PubMed: 16886605]  [MGI Ref ID J:116015]

Li X; Tomita M; Pilbeam CC; Breyer RM; Raisz LG. 2002. Prostaglandin receptor EP2 mediates PGE2 stimulated hypercalcemia in mice in vivo. Prostaglandins Other Lipid Mediat 67(3-4):173-80. [PubMed: 12013525]  [MGI Ref ID J:77679]

Liang X; Wang Q; Hand T; Wu L; Breyer RM; Montine TJ; Andreasson K. 2005. Deletion of the prostaglandin E2 EP2 receptor reduces oxidative damage and amyloid burden in a model of Alzheimer's disease. J Neurosci 25(44):10180-7. [PubMed: 16267225]  [MGI Ref ID J:102728]

Matsumoto H; Ma W; Smalley W; Trzaskos J; Breyer RM; Dey SK. 2001. Diversification of cyclooxygenase-2-derived prostaglandins in ovulation and implantation. Biol Reprod 64(5):1557-65. [PubMed: 11319164]  [MGI Ref ID J:69034]

McCullough L; Wu L; Haughey N; Liang X; Hand T; Wang Q; Breyer RM; Andreasson K. 2004. Neuroprotective function of the PGE2 EP2 receptor in cerebral ischemia. J Neurosci 24(1):257-68. [PubMed: 14715958]  [MGI Ref ID J:87388]

Ochsner SA; Russell DL; Day AJ; Breyer RM; Richards JS. 2003. Decreased expression of tumor necrosis factor-alpha-stimulated gene 6 in cumulus cells of the cyclooxygenase-2 and EP2 null mice. Endocrinology 144(3):1008-19. [PubMed: 12586778]  [MGI Ref ID J:115517]

Ono K; Kaneko H; Choudhary S; Pilbeam CC; Lorenzo JA; Akatsu T; Kugai N; Raisz LG. 2005. Biphasic effect of prostaglandin E2 on osteoclast formation in spleen cell cultures: role of the EP2 receptor. J Bone Miner Res 20(1):23-9. [PubMed: 15619666]  [MGI Ref ID J:101564]

Sadikot RT; Zeng H; Azim AC; Joo M; Dey SK; Breyer RM; Peebles RS; Blackwell TS; Christman JW. 2007. Bacterial clearance of Pseudomonas aeruginosa is enhanced by the inhibition of COX-2. Eur J Immunol 37(4):1001-9. [PubMed: 17330822]  [MGI Ref ID J:120725]

Sheller JR; Mitchell D; Meyrick B; Oates J; Breyer R. 2000. EP(2) receptor mediates bronchodilation by PGE(2) in mice. J Appl Physiol 88(6):2214-8. [PubMed: 10846038]  [MGI Ref ID J:103373]

Shie FS; Breyer RM; Montine TJ. 2005. Microglia Lacking E Prostanoid Receptor Subtype 2 Have Enhanced A{beta} Phagocytosis yet Lack A{beta}-Activated Neurotoxicity. Am J Pathol 166(4):1163-72. [PubMed: 15793296]  [MGI Ref ID J:97062]

Sinha P; Clements VK; Fulton AM; Ostrand-Rosenberg S. 2007. Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 67(9):4507-13. [PubMed: 17483367]  [MGI Ref ID J:121303]

Zhang Y; Guan Y; Schneider A; Brandon S; Breyer RM; Breyer MD. 2000. Characterization of murine vasopressor and vasodepressor prostaglandin E(2) receptors Hypertension 35(5):1129-34. [PubMed: 10818076]  [MGI Ref ID J:62425]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

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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Ordering and Purchasing Information

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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

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