Strain Name:

129.Cg-Ppiatm1Lubn/J

Stock Number:

005320

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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; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Jeremy Luban,   Columbia University

Description
Mice that are homozygous for the targeted mutation are viable, normal in size, and do not display any gross behavioral abnormalities. Homozygotes have reduced fertility. No gene product (protein) is detected by Western blot analysis. Approximately one third of homozygotes spontaneously develop blepharitis (inflammation of the eyelids). Histological examination reveals mononuclear cell, eosinophil and mast cell infiltration of the eyelid. Homozygotes exhibit splenomegaly and elevated levels of total serum IfG1 and IgE. CD4+ T cells isolated from homozygous mice have increased production of IL-2 (3 to 5 times normal) and IL-4. Cultured effector/memory CD4+ T cells are hypersensitive to TCR stimulation and have elevated Th2 cytokine production. This mutant mouse strain may be useful in studies of allergic reactions and effects of cyclosporine on signal transduction.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 1 through 4 and part of exon 5. The construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into MF1 blastocysts. The resulting chimeric animals were crossed to MF1 outbred mice, and then backcrossed to 129S6/SvEvTac for 20 generations.

Control Information

  Control
   Wild-type from the colony
   002448 129S1/SvImJ
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ppiatm1Lubn/Ppiatm1Lubn

        129S6.129P2-Ppiatm1Lubn
  • mortality/aging
  • partial postnatal lethality
    • slight reduction in survival   (MGI Ref ID J:93591)
  • partial prenatal lethality
    • 15% homozygotes born rather than 25% expected when heterozygous parents mated   (MGI Ref ID J:93591)
  • endocrine/exocrine gland phenotype
  • pancreas inflammation
    • eosinophilic infiltrates in the pancreas of some animals with blepharitis   (MGI Ref ID J:93591)
  • hematopoietic system phenotype
  • abnormal CD4-positive, alpha-beta T cell physiology
    • CD4 cells overproduce Il4 and Il2   (MGI Ref ID J:93591)
  • increased T cell number
    • increased numbers of single positive CD4 and CD8 cells but T cell development is otherwise normal   (MGI Ref ID J:93591)
  • increased immunoglobulin level
    • with the exceptions noted, baseline levels of the various isotypes were normal   (MGI Ref ID J:93591)
    • increased IgE level
      • after immunization total IgE was elevated   (MGI Ref ID J:93591)
    • increased IgG1 level
      • baseline levels of IgG1 only were elevated   (MGI Ref ID J:93591)
      • after immunization, antigen specific IgG1 levels were elevated   (MGI Ref ID J:93591)
  • spleen hyperplasia
    • splenocyte numbers are increased 80%   (MGI Ref ID J:93591)
    • spleen architecture otherwise normal   (MGI Ref ID J:93591)
  • immune system phenotype
  • abnormal CD4-positive, alpha-beta T cell physiology
    • CD4 cells overproduce Il4 and Il2   (MGI Ref ID J:93591)
  • increased T cell number
    • increased numbers of single positive CD4 and CD8 cells but T cell development is otherwise normal   (MGI Ref ID J:93591)
  • increased circulating interleukin-4 level
    • elevated levels of Il4   (MGI Ref ID J:93591)
  • increased immunoglobulin level
    • with the exceptions noted, baseline levels of the various isotypes were normal   (MGI Ref ID J:93591)
    • increased IgE level
      • after immunization total IgE was elevated   (MGI Ref ID J:93591)
    • increased IgG1 level
      • baseline levels of IgG1 only were elevated   (MGI Ref ID J:93591)
      • after immunization, antigen specific IgG1 levels were elevated   (MGI Ref ID J:93591)
  • increased inflammatory response
    • eosinophilic infiltrates in the bone marrow of some animals with blepharitis   (MGI Ref ID J:93591)
    • blepharitis
      • swelling and erythema of the eyelid in about 30% of animals   (MGI Ref ID J:93591)
      • appeared about 3 months after birth and worsened with age   (MGI Ref ID J:93591)
      • dense infiltrates of mononuclear cells, eosinophils, and mast cells in subepithelial stroma of conjunctiva and skin   (MGI Ref ID J:93591)
    • heart inflammation
      • eosinophilic infiltrates in the hearts of some animals with blepharitis   (MGI Ref ID J:93591)
    • increased susceptibility to type I hypersensitivity reaction
      • homozygotes develop allergic pathology associated with increased Th2 cytokine production   (MGI Ref ID J:93591)
    • liver inflammation
      • eosinophilic infiltrates in the livers of some animals with blepharitis   (MGI Ref ID J:93591)
    • pancreas inflammation
      • eosinophilic infiltrates in the pancreas of some animals with blepharitis   (MGI Ref ID J:93591)
  • increased interleukin-2 secretion
    • CD4+ T cells overproduce Il2   (MGI Ref ID J:93591)
  • increased interleukin-4 secretion
    • CD4+ T cells cells overproduce Il4   (MGI Ref ID J:93591)
  • spleen hyperplasia
    • splenocyte numbers are increased 80%   (MGI Ref ID J:93591)
    • spleen architecture otherwise normal   (MGI Ref ID J:93591)
  • vision/eye phenotype
  • blepharitis
    • swelling and erythema of the eyelid in about 30% of animals   (MGI Ref ID J:93591)
    • appeared about 3 months after birth and worsened with age   (MGI Ref ID J:93591)
    • dense infiltrates of mononuclear cells, eosinophils, and mast cells in subepithelial stroma of conjunctiva and skin   (MGI Ref ID J:93591)
  • cardiovascular system phenotype
  • heart inflammation
    • eosinophilic infiltrates in the hearts of some animals with blepharitis   (MGI Ref ID J:93591)
  • liver/biliary system phenotype
  • liver inflammation
    • eosinophilic infiltrates in the livers of some animals with blepharitis   (MGI Ref ID J:93591)
  • homeostasis/metabolism phenotype
  • increased circulating interleukin-4 level
    • elevated levels of Il4   (MGI Ref ID J:93591)

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

Ppiatm1Lubn/Ppiatm1Lubn

        involves: 129P2/OlaHsd * MF1
  • mortality/aging
  • partial prenatal lethality
    • slight reduction in embryonic survival   (MGI Ref ID J:93591)
    • 21% homozygotes born rather than 25% expected when heterozygous parents mated   (MGI Ref ID J:93591)
View Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines
Inflammation
Lymphoid Tissue Defects

Research Tools
Immunology, Inflammation and Autoimmunity Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ppiatm1Lubn
Allele Name targeted mutation 1, Jeremy Luban
Allele Type Targeted (Null/Knockout)
Common Name(s) CypA-; Ppia-;
Mutation Made By Jeremy Luban,   Columbia University
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Ppia, peptidylprolyl isomerase A
Chromosome 11
Gene Common Name(s) CYCA; CYPA; CYPH; Cphn; CyP-18; CyP-A; HEL-S-69p; cyclophilin; cyclophilin A;
Molecular Note A neomycin resistance gene replaced all but the last 60 bp of the coding sequence. Immunoblot analysis confirmed absence of protein in thymus, spleen, kidney, and brain. [MGI Ref ID J:64523]

Genotyping

Genotyping Information

Genotyping Protocols

Ppiatm1Lubn, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Colgan J; Asmal M; Neagu M; Yu B; Schneidkraut J; Lee Y; Sokolskaja E; Andreotti A; Luban J. 2004. Cyclophilin A regulates TCR signal strength in CD4+ T cells via a proline-directed conformational switch in Itk. Immunity 21(2):189-201. [PubMed: 15308100]  [MGI Ref ID J:93591]

Additional References

Ppiatm1Lubn related

Bell RD; Winkler EA; Singh I; Sagare AP; Deane R; Wu Z; Holtzman DM; Betsholtz C; Armulik A; Sallstrom J; Berk BC; Zlokovic BV. 2012. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485(7399):512-6. [PubMed: 22622580]  [MGI Ref ID J:184835]

Colgan J; Asmal M; Luban J. 2000. Isolation, characterization and targeted disruption of mouse ppia: cyclophilin A is not essential for mammalian cell viability Genomics 68(2):167-78. [PubMed: 10964515]  [MGI Ref ID J:64523]

Colgan J; Asmal M; Yu B; Luban J. 2005. Cyclophilin A-deficient mice are resistant to immunosuppression by cyclosporine. J Immunol 174(10):6030-8. [PubMed: 15879096]  [MGI Ref ID J:98990]

Dear JW; Simpson KJ; Nicolai MP; Catterson JH; Street J; Huizinga T; Craig DG; Dhaliwal K; Webb S; Bateman DN; Webb DJ. 2011. Cyclophilin A is a damage-associated molecular pattern molecule that mediates acetaminophen-induced liver injury. J Immunol 187(6):3347-52. [PubMed: 21824865]  [MGI Ref ID J:179263]

Dorner M; Horwitz JA; Donovan BM; Labitt RN; Budell WC; Friling T; Vogt A; Catanese MT; Satoh T; Kawai T; Akira S; Law M; Rice CM; Ploss A. 2013. Completion of the entire hepatitis C virus life cycle in genetically humanized mice. Nature 501(7466):237-41. [PubMed: 23903655]  [MGI Ref ID J:205017]

Elvers M; Herrmann A; Seizer P; Munzer P; Beck S; Schonberger T; Borst O; Martin-Romero FJ; Lang F; May AE; Gawaz M. 2012. Intracellular cyclophilin A is an important Ca(2+) regulator in platelets and critically involved in arterial thrombus formation. Blood 120(6):1317-26. [PubMed: 22740452]  [MGI Ref ID J:189184]

Nigro P; Satoh K; O'Dell MR; Soe NN; Cui Z; Mohan A; Abe J; Alexis JD; Sparks JD; Berk BC. 2011. Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E-deficient mice. J Exp Med 208(1):53-66. [PubMed: 21173104]  [MGI Ref ID J:176860]

Satoh K; Matoba T; Suzuki J; O'Dell MR; Nigro P; Cui Z; Mohan A; Pan S; Li L; Jin ZG; Yan C; Abe J; Berk BC. 2008. Cyclophilin A mediates vascular remodeling by promoting inflammation and vascular smooth muscle cell proliferation. Circulation 117(24):3088-98. [PubMed: 18541741]  [MGI Ref ID J:155079]

Satoh K; Nigro P; Matoba T; O'Dell MR; Cui Z; Shi X; Mohan A; Yan C; Abe J; Illig KA; Berk BC. 2009. Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II-induced aortic aneurysms. Nat Med 15(6):649-56. [PubMed: 19430489]  [MGI Ref ID J:151171]

Satoh K; Nigro P; Zeidan A; Soe NN; Jaffre F; Oikawa M; O'Dell MR; Cui Z; Menon P; Lu Y; Mohan A; Yan C; Blaxall BC; Berk BC. 2011. Cyclophilin A promotes cardiac hypertrophy in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 31(5):1116-23. [PubMed: 21330604]  [MGI Ref ID J:191491]

Seizer P; Klingel K; Sauter M; Westermann D; Ochmann C; Schonberger T; Schleicher R; Stellos K; Schmidt EM; Borst O; Bigalke B; Kandolf R; Langer H; Gawaz M; May AE. 2012. Cyclophilin A affects inflammation, virus elimination and myocardial fibrosis in coxsackievirus B3-induced myocarditis. J Mol Cell Cardiol 53(1):6-14. [PubMed: 22446162]  [MGI Ref ID J:185733]

Seizer P; Ochmann C; Schonberger T; Zach S; Rose M; Borst O; Klingel K; Kandolf R; MacDonald HR; Nowak RA; Engelhardt S; Lang F; Gawaz M; May AE. 2011. Disrupting the EMMPRIN (CD147)-cyclophilin A interaction reduces infarct size and preserves systolic function after myocardial ischemia and reperfusion. Arterioscler Thromb Vasc Biol 31(6):1377-86. [PubMed: 21441138]  [MGI Ref ID J:191475]

Zhu C; Wang X; Deinum J; Huang Z; Gao J; Modjtahedi N; Neagu MR; Nilsson M; Eriksson PS; Hagberg H; Luban J; Kroemer G; Blomgren K. 2007. Cyclophilin A participates in the nuclear translocation of apoptosis-inducing factor in neurons after cerebral hypoxia-ischemia. J Exp Med 204(8):1741-8. [PubMed: 17635954]  [MGI Ref ID J:125956]

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 strain is maintained as a heterozygote due to reduced fertility of homozygotes.
Diet Information LabDiet® 5K52/5K67

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 will fulfill 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 will fulfill 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
   Wild-type from the colony
   002448 129S1/SvImJ
 
  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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"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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