Strain Name:

B6.129-P2rx2tm1Ckn/J

Stock Number:

004603

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Debra A Cockayne,   Roche Bioscience

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by RT-PCR of intestinal tissue or Western blot analysis of dorsal root and trigeminal ganglia. No immunoreactive staining was detected in ileum by immunohistochemical analysis. Myenteric neurons exhibit altered intracellular electrophysiological action potentials. Fast excitatory postsynaptic potentials (fEPSPs) from mutant S neurons (myenteric plexus interneurons and motorneurons) are inhibited by the nicotinic cholinergic receptor antagonist, mecamylamine. ATP-induced depolarization of isolated mutant S neurons is abolished. Peristalsis is impaired in the ileum. Mutant mice ventilatory response to hypoxia is diminished, as determined by in vitro carotid sinus nerve preparation. ATP and ATP analog (alpha,beta-methyleneATP) elicits a faster discharge (afferent activity) in mutant sinus nerves. This mutant mouse strain may be useful in studies related to pain and peripheral nerve hypersensitivity, and sensory perception.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 2 through 11. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Deafness, Autosomal Dominant 41; DFNA41   (P2RX2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

P2rx2tm1Ckn/P2rx2tm1Ckn

        involves: 129P2/OlaHsd * C57BL/6
  • respiratory system phenotype
  • decreased pulmonary ventilation
    • in response to hypoxia (10% O2), adult homozygotes (4-6 months of age) display a significantly reduced ventilatory response showing an increase of only 261 +/- 202 ml/min/kg in minute ventilation (VE) relative to 1008 +/- 154 ml/min/kg in wild-type controls   (MGI Ref ID J:86890)
    • in response to further hypoxia (7.5% O2), homozygotes display a severe ventilatory depression with the VE reduced below prehypoxic levels by 606 +/- 209 ml/min/kg, unlike wild-type controls where no additional increase in ventilation is observed but the VE remains above normoxic levels   (MGI Ref ID J:86890)
    • however, adult homozygotes display normal resting ventilation during normoxia and show normal ventilatory responses to a mild (15% O2) hypoxia relative to wild-type controls   (MGI Ref ID J:86890)
  • cardiovascular system phenotype
  • abnormal carotid body physiology
    • homozygotes show a dramatic reduction in afferent nerve responses of the carotid sinus nerve to a decrease in oxygen tension (PO2)   (MGI Ref ID J:86890)
    • unlike in in vitro carotid body-sinus nerve preparations from wild-type mice where sinus nerve discharge increases from baseline to a peak of 130.82 +/- 10.79 spikes/sec during hypoxia, the afferent discharge in preparations from mutant mice only reaches a peak of 58.13 +/- 9.40 spikes/sec, indicating that carotid body function is impaired   (MGI Ref ID J:86890)
    • the average peak firing rate of single units induced by hypoxia is significantly lower in carotid body-sinus nerve preparations from mutant mice (1.64 +/- 0.11 spikes/sec) relative to that observed in wild-type preparations (7.96 +/- 0.88 spikes/sec)   (MGI Ref ID J:86890)
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • in response to hypoxia (7.5% O2), adult homozygotes display normal decreases in body temperature relative to wild-type controls (0.9 +/- 0.2 vs 0.8 +/- 0.1 degress Celsius, respectively)   (MGI Ref ID J:86890)
  • nervous system phenotype
  • abnormal carotid body physiology
    • homozygotes show a dramatic reduction in afferent nerve responses of the carotid sinus nerve to a decrease in oxygen tension (PO2)   (MGI Ref ID J:86890)
    • unlike in in vitro carotid body-sinus nerve preparations from wild-type mice where sinus nerve discharge increases from baseline to a peak of 130.82 +/- 10.79 spikes/sec during hypoxia, the afferent discharge in preparations from mutant mice only reaches a peak of 58.13 +/- 9.40 spikes/sec, indicating that carotid body function is impaired   (MGI Ref ID J:86890)
    • the average peak firing rate of single units induced by hypoxia is significantly lower in carotid body-sinus nerve preparations from mutant mice (1.64 +/- 0.11 spikes/sec) relative to that observed in wild-type preparations (7.96 +/- 0.88 spikes/sec)   (MGI Ref ID J:86890)
View Research Applications

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

P2rx2tm1Ckn related

Internal/Organ Research
Gastrointestinal Defects

Neurobiology Research
Channel and Transporter Defects
Neuromuscular Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol P2rx2tm1Ckn
Allele Name targeted mutation 1, Debra A Cockayne
Allele Type Targeted (Null/Knockout)
Common Name(s) P2X2-;
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14.1
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name P2rx2, purinergic receptor P2X, ligand-gated ion channel, 2
Chromosome 5
Gene Common Name(s) DFNA41; P2X2; P2X2a;
Molecular Note Exons 2 through 11 were deleted and replaced by a neomycin resistance cassette by homologous recombination in ES cells. RT-PCR analysis confirmed absence of mRNA in whole brain and testis from homozygous mutant mice, whereas the expected band was obtained in wild-type mice. [MGI Ref ID J:88199]

Genotyping

Genotyping Information

Genotyping Protocols

P2rx2tm1Ckn, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Ren J; Bian X; DeVries M; Schnegelsberg B; Cockayne DA; Ford AP; Galligan JJ. 2003. P2X2 subunits contribute to fast synaptic excitation in myenteric neurons of the mouse small intestine. J Physiol 552(Pt 3):809-21. [PubMed: 12937291]  [MGI Ref ID J:105504]

Additional References

Rong W; Gourine AV; Cockayne DA; Xiang Z; Ford AP; Spyer KM; Burnstock G. 2003. Pivotal role of nucleotide P2X2 receptor subunit of the ATP-gated ion channel mediating ventilatory responses to hypoxia. J Neurosci 23(36):11315-21. [PubMed: 14672995]  [MGI Ref ID J:86890]

P2rx2tm1Ckn related

Cockayne DA; Dunn PM; Zhong Y; Rong W; Hamilton SG; Knight GE; Ruan HZ; Ma B; Yip P; Nunn P; McMahon SB; Burnstock G; Ford AP. 2005. P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP. J Physiol 567(Pt 2):621-39. [PubMed: 15961431]  [MGI Ref ID J:112498]

Di Paolo NC; Miao EA; Iwakura Y; Murali-Krishna K; Aderem A; Flavell RA; Papayannopoulou T; Shayakhmetov DM. 2009. Virus binding to a plasma membrane receptor triggers interleukin-1 alpha-mediated proinflammatory macrophage response in vivo. Immunity 31(1):110-21. [PubMed: 19576795]  [MGI Ref ID J:151628]

Finger TE; Danilova V; Barrows J; Bartel DL; Vigers AJ; Stone L; Hellekant G; Kinnamon SC. 2005. ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 310(5753):1495-9. [PubMed: 16322458]  [MGI Ref ID J:103231]

Housley GD; Morton-Jones R; Vlajkovic SM; Telang RS; Paramananthasivam V; Tadros SF; Wong AC; Froud KE; Cederholm JM; Sivakumaran Y; Snguanwongchai P; Khakh BS; Cockayne DA; Thorne PR; Ryan AF. 2013. ATP-gated ion channels mediate adaptation to elevated sound levels. Proc Natl Acad Sci U S A 110(18):7494-9. [PubMed: 23592720]  [MGI Ref ID J:196658]

Huang YA; Stone LM; Pereira E; Yang R; Kinnamon JC; Dvoryanchikov G; Chaudhari N; Finger TE; Kinnamon SC; Roper SD. 2011. Knocking out P2X receptors reduces transmitter secretion in taste buds. J Neurosci 31(38):13654-61. [PubMed: 21940456]  [MGI Ref ID J:177120]

Khakh BS; Gittermann D; Cockayne DA; Jones A. 2003. ATP modulation of excitatory synapses onto interneurons. J Neurosci 23(19):7426-37. [PubMed: 12917379]  [MGI Ref ID J:88199]

Navarro B; Miki K; Clapham DE. 2011. ATP-activated P2X2 current in mouse spermatozoa. Proc Natl Acad Sci U S A 108(34):14342-7. [PubMed: 21831833]  [MGI Ref ID J:175979]

Rong W; Gourine AV; Cockayne DA; Xiang Z; Ford AP; Spyer KM; Burnstock G. 2003. Pivotal role of nucleotide P2X2 receptor subunit of the ATP-gated ion channel mediating ventilatory responses to hypoxia. J Neurosci 23(36):11315-21. [PubMed: 14672995]  [MGI Ref ID J:86890]

Ryten M; Koshi R; Knight GE; Turmaine M; Dunn P; Cockayne DA; Ford AP; Burnstock G. 2007. Abnormalities in neuromuscular junction structure and skeletal muscle function in mice lacking the P2X2 nucleotide receptor. Neuroscience 148(3):700-11. [PubMed: 17706883]  [MGI Ref ID J:128394]

Stratford JM; Finger TE. 2011. Central representation of postingestive chemosensory cues in mice that lack the ability to taste. J Neurosci 31(25):9101-10. [PubMed: 21697361]  [MGI Ref ID J:173522]

Yan D; Zhu Y; Walsh T; Xie D; Yuan H; Sirmaci A; Fujikawa T; Wong AC; Loh TL; Du L; Grati M; Vlajkovic SM; Blanton S; Ryan AF; Chen ZY; Thorne PR; Kachar B; Tekin M; Zhao HB; Housley GD; King MC; Liu XZ. 2013. Mutation of the ATP-gated P2X(2) receptor leads to progressive hearing loss and increased susceptibility to noise. Proc Natl Acad Sci U S A 110(6):2228-33. [PubMed: 23345450]  [MGI Ref ID J:194332]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryThe resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to C57BL/6J for 6 generations (using a speed congenic protocol) before being made homozygous. When maintaining a live colony, these mice are bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. 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, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We willfulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. 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, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We willfulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

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 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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