Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N7pF9 (14-OCT-08)   Donating Investigator Christopher Gabel,   Pfizer Pharmaceuticals

Description
Mice that are homozygous for the targeted allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected in cultured bone marrow mast cells or peritoneal macrophages. Samples of whole blood, as well as peritoneal macrophages, derived from mutant mice fail to produce extracellular interleukin 1 beta in response to lipopolysaccharide (LPS) and ATP treatment. Similarly, peritoneal lavage fluids from mutant animals that have been primed with LPS and subsequently challenged with ATP, are deficient in mature interleukin 1 beta, and at later time points, exhibit attenuated interleukin 6 levels when compared to fluids from similarly treated wildtype mice. Peripheral blood monocytes and leukocytes fail to change shape/volume and shed L-selectin in response to ATP. Mutant mice exhibit reduced induction and severity of monoclonal anti-collagen-induced arthritis. Mutant mice also display significant reduction in femoral periosteal circumference, reduced periosteal bone formation, and a reduction in total and cortical bone content. Increased resorption in tibial trabecular bone tissue is observed. This mutant mouse strain may be useful in studies examining the consequences of disrupted interleukin 1 beta processing and the regulation of bone formation and resorption.

Development
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt the carboxyl-terminal coding region of the targeted gene. The construct was electroporated into 129P2/OlaHsd-derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric animals were backcrossed to C57BL/6 mice for 7 generations.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

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.

P2rx7^tm1Gab/P2rx7^tm1Gab

        either: (involves: 129P2/OlaHsd * C57BL/6) or (involves: 129P2/OlaHsd * C57BL/6 * DBA/2)

• cellular phenotype
• abnormal cell death (MGI Ref ID J:89513)
  • lysis triggered by extracellular ATP does not occur
• growth/size phenotype
• decreased body weight (MGI Ref ID J:84145)
  • although body weight was normal in males at birth, it was about 16% less than normal at 9 months of age
• immune system phenotype
• abnormal interleukin physiology (MGI Ref ID J:66835)
• abnormal interleukin-6 secretion (MGI Ref ID J:66835)
  • IL-6 release as a result of ATP challenge as opposed to PBS challenge increases similar to wild-type mice after 30 minutes
  • 120 minutes after ATP challenge, IL-6 release drops as compared to continued increase in wild-type mice, although still greater than after a PBS challenge
• decreased interleukin-1 beta secretion (MGI Ref ID J:66835)
  • although pro-Il1beta is produced by peritoneal machrophages, no mature IL-1beta is produced or released as a result of ATP challenge
• increased osteoclast cell number (MGI Ref ID J:84145)
  • increased number of osteoclasts in tibial trabecular bone
• limbs/digits/tail phenotype
• decreased diameter of long bones (MGI Ref ID J:84145)
  • diameters of femurs and tibia were reduced although lengths were normal
• decreased diameter of femur (MGI Ref ID J:89513)
• decreased diameter of tibia (MGI Ref ID J:89513)
• skeleton phenotype
• abnormal skeleton development (MGI Ref ID J:84145)
  • lower total bone content
• abnormal skeleton physiology (MGI Ref ID J:84145)
  • reduced periosteal bone expansion in long bones
• decreased diameter of long bones (MGI Ref ID J:84145)
  • diameters of femurs and tibia were reduced although lengths were normal
• decreased diameter of femur (MGI Ref ID J:89513)
• decreased diameter of tibia (MGI Ref ID J:89513)
• increased osteoclast cell number (MGI Ref ID J:84145)
  • increased number of osteoclasts in tibial trabecular bone
• hematopoietic system phenotype
• increased osteoclast cell number (MGI Ref ID J:84145)
  • increased number of osteoclasts in tibial trabecular bone

View Research Applications

Research Applications

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

Developmental Biology Research
Skeletal Defects

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines

Genes & Alleles

Gene & Allele Information

Allele Symbol		P2rx7tm1Gab
Allele Name		targeted mutation 1, Christopher A Gabel
Allele Type		Targeted (knock-out)
Common Name(s)		P2X7 KO; P2X7-; P2X7R-; P2X7RDelta506-532);
Mutation Made By		Patrick Gillespie,   Pfizer Pharmaceuticals
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14TG2a
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		P2rx7, purinergic receptor P2X, ligand-gated ion channel, 7
Chromosome		5
Gene Common Name(s)		AI467586; MGC20089; P2X7; P2X7 receptor; P2X7R; expressed sequence AI467586;
Molecular Note		Sequence encoding amino acids 506 through 532 was replaced by the insertion of a neomycin selection cassette. Transcript was undetected by Northern blot analysis of bone marrow mast cells isolated from homozygous mutant mice. Western blot analysis of homozygous mutant peritoneal macrophages showed an absence of normal and truncated protein. [MGI Ref ID J:66835]

Genotyping

Genotyping Information

Genotyping Protocols

P2rx7^tm1Gab, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Solle M; Labasi J; Perregaux DG; Stam E; Petrushova N; Koller BH; Griffiths RJ; Gabel CA. 2001. Altered cytokine production in mice lacking P2X(7) receptors. J Biol Chem 276(1):125-32. [PubMed: 11016935]  [MGI Ref ID J:66835]

Additional References

P2rx7^tm1Gab related

Aswad F; Dennert G. 2006. P2X(7) receptor expression levels determine lethal effects of a purine based danger signal in T lymphocytes. Cell Immunol 243(1):58-65. [PubMed: 17286969]  [MGI Ref ID J:118682]

Aswad F; Kawamura H; Dennert G. 2005. High sensitivity of CD4+CD25+ regulatory T cells to extracellular metabolites nicotinamide adenine dinucleotide and ATP: a role for P2X7 receptors. J Immunol 175(5):3075-83. [PubMed: 16116196]  [MGI Ref ID J:113208]

Auger R; Motta I; Benihoud K; Ojcius DM; Kanellopoulos JM. 2005. A role for mitogen-activated protein kinase(Erk1/2) activation and non-selective pore formation in P2X7 receptor-mediated thymocyte death. J Biol Chem 280(30):28142-51. [PubMed: 15937334]  [MGI Ref ID J:100823]

Chen L; Brosnan CF. 2006. Exacerbation of experimental autoimmune encephalomyelitis in P2X7R-/- mice: evidence for loss of apoptotic activity in lymphocytes. J Immunol 176(5):3115-26. [PubMed: 16493071]  [MGI Ref ID J:129413]

Cowley SC; Hamilton E; Frelinger JA; Su J; Forman J; Elkins KL. 2005. CD4-CD8- T cells control intracellular bacterial infections both in vitro and in vivo. J Exp Med 202(2):309-19. [PubMed: 16027239]  [MGI Ref ID J:100513]

Franke H; Klimke K; Brinckmann U; Grosche J; Francke M; Sperlagh B; Reichenbach A; Liebert UG; Illes P. 2005. P2X(7) receptor-mRNA and -protein in the mouse retina; changes during retinal degeneration in BALBCrds mice. Neurochem Int 47(4):235-42. [PubMed: 15964665]  [MGI Ref ID J:103892]

Garcia-Marcos M; Fontanils U; Aguirre A; Pochet S; Dehaye JP; Marino A. 2005. Role of sodium in mitochondrial membrane depolarization induced by P2X7 receptor activation in submandibular glands. FEBS Lett 579(24):5407-13. [PubMed: 16198349]  [MGI Ref ID J:102387]

Goncalves RG; Gabrich L; Rosario A Jr; Takiya CM; Ferreira ML; Chiarini LB; Persechini PM; Coutinho-Silva R; Leite M Jr. 2006. The role of purinergic P2X7 receptors in the inflammation and fibrosis of unilateral ureteral obstruction in mice. Kidney Int 70(9):1599-606. [PubMed: 16969386]  [MGI Ref ID J:136485]

Heiss K; Janner N; Mahnss B; Schumacher V; Koch-Nolte F; Haag F; Mittrucker HW. 2008. High sensitivity of intestinal CD8+ T cells to nucleotides indicates P2X7 as a regulator for intestinal T cell responses. J Immunol 181(6):3861-9. [PubMed: 18768840]  [MGI Ref ID J:139109]

Kawamura H; Aswad F; Minagawa M; Govindarajan S; Dennert G. 2006. P2X7 receptors regulate NKT cells in autoimmune hepatitis. J Immunol 176(4):2152-60. [PubMed: 16455971]  [MGI Ref ID J:129123]

Ke HZ; Qi H; Weidema AF; Zhang Q; Panupinthu N; Crawford DT; Grasser WA; Paralkar VM; Li M; Audoly LP; Gabel CA; Jee WS; Dixon SJ; Sims SM; Thompson DD. 2003. Deletion of the P2X7 nucleotide receptor reveals its regulatory roles in bone formation and resorption. Mol Endocrinol 17(7):1356-67. [PubMed: 12677010]  [MGI Ref ID J:84145]

Labasi JM; Petrushova N; Donovan C; McCurdy S; Lira P; Payette MM; Brissette W; Wicks JR; Audoly L; Gabel CA. 2002. Absence of the P2X7 receptor alters leukocyte function and attenuates an inflammatory response. J Immunol 168(12):6436-45. [PubMed: 12055263]  [MGI Ref ID J:111397]

Le Stunff H; Auger R; Kanellopoulos J; Raymond MN. 2004. The Pro-451 to Leu polymorphism within the C-terminal tail of P2X7 receptor impairs cell death but not phospholipase D activation in murine thymocytes. J Biol Chem 279(17):16918-26. [PubMed: 14761980]  [MGI Ref ID J:89513]

Li J; Liu D; Ke HZ; Duncan RL; Turner CH. 2005. The P2X7 nucleotide receptor mediates skeletal mechanotransduction. J Biol Chem 280(52):42952-9. [PubMed: 16269410]  [MGI Ref ID J:105908]

Marin-Garcia P; Sanchez-Nogueiro J; Gomez-Villafuertes R; Leon D; Miras-Portugal MT. 2008. Synaptic terminals from mice midbrain exhibit functional P2X(7) receptor. Neuroscience 151(2):361-73. [PubMed: 18082965]  [MGI Ref ID J:130842]

Myers AJ; Eilertson B; Fulton SA; Flynn JL; Canaday DH. 2005. The purinergic P2X7 receptor is not required for control of pulmonary Mycobacterium tuberculosis infection. Infect Immun 73(5):3192-5. [PubMed: 15845532]  [MGI Ref ID J:97621]

Niessen F; Schaffner F; Furlan-Freguia C; Pawlinski R; Bhattacharjee G; Chun J; Derian CK; Andrade-Gordon P; Rosen H; Ruf W. 2008. Dendritic cell PAR1-S1P3 signalling couples coagulation and inflammation. Nature 452(7187):654-8. [PubMed: 18305483]  [MGI Ref ID J:133917]

Panupinthu N; Rogers JT; Zhao L; Solano-Flores LP; Possmayer F; Sims SM; Dixon SJ. 2008. P2X7 receptors on osteoblasts couple to production of lysophosphatidic acid: a signaling axis promoting osteogenesis. J Cell Biol 181(5):859-71. [PubMed: 18519738]  [MGI Ref ID J:137037]

Panupinthu N; Zhao L; Possmayer F; Ke HZ; Sims SM; Dixon SJ. 2007. P2X7 nucleotide receptors mediate blebbing in osteoblasts through a pathway involving lysophosphatidic acid. J Biol Chem 282(5):3403-12. [PubMed: 17135244]  [MGI Ref ID J:120291]

Papp L; Vizi ES; Sperlagh B. 2004. Lack of ATP-evoked GABA and glutamate release in the hippocampus of P2X7 receptor-/- mice. Neuroreport 15(15):2387-91. [PubMed: 15640761]  [MGI Ref ID J:103703]

Sanchez-Nogueiro J; Marin-Garcia P; Miras-Portugal MT. 2005. Characterization of a functional P2X(7)-like receptor in cerebellar granule neurons from P2X(7) knockout mice. FEBS Lett 579(17):3783-8. [PubMed: 15978588]  [MGI Ref ID J:99778]

Sim JA; Young MT; Sung HY; North RA; Surprenant A. 2004. Reanalysis of P2X7 receptor expression in rodent brain. J Neurosci 24(28):6307-14. [PubMed: 15254086]  [MGI Ref ID J:97270]

Taylor SR; Gonzalez-Begne M; Dewhurst S; Chimini G; Higgins CF; Melvin JE; Elliott JI. 2008. Sequential shrinkage and swelling underlie P2X7-stimulated lymphocyte phosphatidylserine exposure and death. J Immunol 180(1):300-8. [PubMed: 18097031]  [MGI Ref ID J:130933]

Tourneur L; Mistou S; Schmitt A; Chiocchia G. 2008. Adenosine receptors control a new pathway of Fas-associated death domain protein expression regulation by secretion. J Biol Chem 283(26):17929-38. [PubMed: 18445587]  [MGI Ref ID J:138177]

Witting A; Chen L; Cudaback E; Straiker A; Walter L; Rickman B; Moller T; Brosnan C; Stella N. 2006. Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection. Proc Natl Acad Sci U S A 103(16):6362-7. [PubMed: 16571660]  [MGI Ref ID J:109031]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes
Mating System	Homozygote 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
	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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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

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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

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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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