Strain Name:

C.129-Btlatm1Kmm/J

Stock Number:

006339

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Availability:

Cryopreserved - Ready for recovery

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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.
GenerationN10+N1F2pN1
Generation Definitions
 
Donating InvestigatorDr. Kenneth Murphy,   Washingston Univ School of Medicine

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) is detected by Northern blot analysis of splenocytes isolated from homozygous animals. Mutant mice exhibit increased sensitivity to antigen-induced experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. T-cell proliferation is enhanced in response to antigen challenge. Although acute experimental allergic airway inflammation intensity is only slightly increased, the response duration is significantly prolonged. This mutant mouse strain may be useful in studies of immune response and autoimmunity, and in transplantation studies.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector containing a loxP site flanked neomycin resistance cassette and a herpes simplex virus thymidine kinase gene was used to disrupt exons 3, 4, 5 and part of exon 6 of the endogenous gene. The construct was electroporated into 129/SvEv derived embryonic stem (ES) cells, and correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to BALB/c mice, and then backcrossed to the same for 10 generations.

Control Information

  Control
   000651 BALB/cJ
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Btlatm1Kmm allele
006353   B6.129-Btlatm1Kmm/J
006355   NOD.129-Btlatm1Kmm/J
View Strains carrying   Btlatm1Kmm     (2 strains)

Phenotype

Phenotype Information

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.

Btlatm1Kmm/Btlatm1Kmm

        involves: 129S/SvEv
  • immune system phenotype
  • abnormal humoral immune response
    • 4 weeks after immunization with nitrophenol-conjugated keyhole limpet hemocyanin (NP-KLH), mice show a 3-fold increase in the levels of NP-KLH specific IgG1, IgG2a and IgG2b   (MGI Ref ID J:84084)
    • increased IgG1 level
      • 3-fold increase compared to wild-type in response to NP-KLH immunization   (MGI Ref ID J:84084)
    • increased IgG2a level
      • 3-fold increase compared to wild-type in response to NP-KLH immunization   (MGI Ref ID J:84084)
    • increased IgG2b level
      • 3-fold increase compared to wild-type in response to NP-KLH immunization   (MGI Ref ID J:84084)
  • increased B cell proliferation
    • B cells show a slightly greater proliferative response to stimulation with anti-IgM   (MGI Ref ID J:84084)
  • increased T cell proliferation
    • T cells show a heightened proliferative response to stimulation with anti-CD3 antibody   (MGI Ref ID J:84084)
  • increased susceptibility to experimental autoimmune encephalomyelitis
    • mutants show increased clinical score, earlier onset, and prolonged duration of experimentally induced autoimmune encephalomyelitis compared to wild-type   (MGI Ref ID J:84084)
  • hematopoietic system phenotype
  • increased B cell proliferation
    • B cells show a slightly greater proliferative response to stimulation with anti-IgM   (MGI Ref ID J:84084)
  • increased IgG1 level
    • 3-fold increase compared to wild-type in response to NP-KLH immunization   (MGI Ref ID J:84084)
  • increased IgG2a level
    • 3-fold increase compared to wild-type in response to NP-KLH immunization   (MGI Ref ID J:84084)
  • increased IgG2b level
    • 3-fold increase compared to wild-type in response to NP-KLH immunization   (MGI Ref ID J:84084)
  • increased T cell proliferation
    • T cells show a heightened proliferative response to stimulation with anti-CD3 antibody   (MGI Ref ID J:84084)

Btlatm1Kmm/Btlatm1Kmm

        B6.129S-Btlatm1Kmm
  • immune system phenotype
  • abnormal T cell activation
    • splenocytes in mice receiving a Bm12 to B6 allograft show significantly higher anti-donor responder frequencies when challenged with Bm12 antigen presenting cells   (MGI Ref ID J:119356)
    • decreased T cell proliferation
      • marginal decrease in proliferation of CD8+ T cells, and no decrease in CD4+ T cells, stimulated with fully MHC mismatched cells   (MGI Ref ID J:119356)
    • increased T cell proliferation
      • increased proliferation of CD4+ T cells stimulated with MHC class II antigens   (MGI Ref ID J:119356)
      • splenocytes adoptively transfered into irradiated Bm12 hosts enter the cell cycle and undergo multiple rounds of division within 72 hours, unlike wild-type cells   (MGI Ref ID J:119356)
      • CD8+ T cells show a marginal increase in proliferation in response to MHC class II antigens   (MGI Ref ID J:119356)
      • however, cells receiving strong alloreactive stimulation show little difference from wild-type cells   (MGI Ref ID J:119356)
  • decreased interferon-gamma secretion
    • reduced production of IFNG by alloreactive T cells in response to strong alloactivation (full MHC mismatch)   (MGI Ref ID J:119356)
  • decreased interleukin-2 secretion
    • reduced production of IL2 by alloreactive T cells in response to strong alloactivation (full MHC mismatch)   (MGI Ref ID J:119356)
  • increased length of allograft survival
    • increases survival of fully MHC-mismatched cardiac allografts (12 +/- 5 days) compared to wild-type (8 +/- 1 days)   (MGI Ref ID J:119356)
    • treatment with rapamycin significantly prolongs allograft survival (53 +/- 12 days) compared to treated wild-type (11 +/- 2 days)   (MGI Ref ID J:119356)
  • hematopoietic system phenotype
  • abnormal T cell activation
    • splenocytes in mice receiving a Bm12 to B6 allograft show significantly higher anti-donor responder frequencies when challenged with Bm12 antigen presenting cells   (MGI Ref ID J:119356)
    • decreased T cell proliferation
      • marginal decrease in proliferation of CD8+ T cells, and no decrease in CD4+ T cells, stimulated with fully MHC mismatched cells   (MGI Ref ID J:119356)
    • increased T cell proliferation
      • increased proliferation of CD4+ T cells stimulated with MHC class II antigens   (MGI Ref ID J:119356)
      • splenocytes adoptively transfered into irradiated Bm12 hosts enter the cell cycle and undergo multiple rounds of division within 72 hours, unlike wild-type cells   (MGI Ref ID J:119356)
      • CD8+ T cells show a marginal increase in proliferation in response to MHC class II antigens   (MGI Ref ID J:119356)
      • however, cells receiving strong alloreactive stimulation show little difference from wild-type cells   (MGI Ref ID J:119356)
View Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
      experimental allergic encephalomyelitis (EAE)
Immunodeficiency
      defects in humoral immune responses

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Btlatm1Kmm
Allele Name targeted mutation 1, Kenneth M Murphy
Allele Type Targeted (Null/Knockout)
Common Name(s) BTLA-;
Mutation Made ByDr. Kenneth Murphy,   Washingston Univ School of Medicine
Strain of Origin129S/SvEv
Gene Symbol and Name Btla, B and T lymphocyte associated
Chromosome 16
Gene Common Name(s) BTLA1; CD272;
Molecular Note A genomic region containing exons 3, 4 and 5 was replaced with a neomycin selection cassette through homologous recombination. Northern blot analysis on splenocytes derived from homozygous mice demonstrated that no detectable transcript was expressed from this allele. [MGI Ref ID J:84084]

Genotyping

Genotyping Information

Genotyping Protocols

Btlatm1Kmm, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Btlatm1Kmm related

De Trez C; Schneider K; Potter K; Droin N; Fulton J; Norris PS; Ha SW; Fu YX; Murphy T; Murphy KM; Pfeffer K; Benedict CA; Ware CF. 2008. The inhibitory HVEM-BTLA pathway counter regulates lymphotoxin receptor signaling to achieve homeostasis of dendritic cells. J Immunol 180(1):238-48. [PubMed: 18097025]  [MGI Ref ID J:130896]

Deppong C; Degnan JM; Murphy TL; Murphy KM; Green JM. 2008. B and T lymphocyte attenuator regulates T cell survival in the lung. J Immunol 181(5):2973-9. [PubMed: 18713967]  [MGI Ref ID J:138965]

Deppong C; Juehne TI; Hurchla M; Friend LD; Shah DD; Rose CM; Bricker TL; Shornick LP; Crouch EC; Murphy TL; Holtzman MJ; Murphy KM; Green JM. 2006. Cutting edge: B and T lymphocyte attenuator and programmed death receptor-1 inhibitory receptors are required for termination of acute allergic airway inflammation. J Immunol 176(7):3909-13. [PubMed: 16547224]  [MGI Ref ID J:129881]

Hurchla MA; Sedy JR; Gavrielli M; Drake CG; Murphy TL; Murphy KM. 2005. B and T lymphocyte attenuator exhibits structural and expression polymorphisms and is highly Induced in anergic CD4+ T cells. J Immunol 174(6):3377-85. [PubMed: 15749870]  [MGI Ref ID J:97696]

Iwata A; Watanabe N; Oya Y; Owada T; Ikeda K; Suto A; Kagami S; Hirose K; Kanari H; Kawashima S; Nakayama T; Taniguchi M; Iwamoto I; Nakajima H. 2010. Protective roles of B and T lymphocyte attenuator in NKT cell-mediated experimental hepatitis. J Immunol 184(1):127-33. [PubMed: 19949073]  [MGI Ref ID J:159040]

Kashiwakuma D; Suto A; Hiramatsu Y; Ikeda K; Takatori H; Suzuki K; Kagami S; Hirose K; Watanabe N; Iwamoto I; Nakajima H. 2010. B and T lymphocyte attenuator suppresses IL-21 production from follicular Th cells and subsequent humoral immune responses. J Immunol 185(5):2730-6. [PubMed: 20660710]  [MGI Ref ID J:163268]

Kobayashi Y; Iwata A; Suzuki K; Suto A; Kawashima S; Saito Y; Owada T; Kobayashi M; Watanabe N; Nakajima H. 2013. B and T lymphocyte attenuator inhibits LPS-induced endotoxic shock by suppressing Toll-like receptor 4 signaling in innate immune cells. Proc Natl Acad Sci U S A 110(13):5121-6. [PubMed: 23479601]  [MGI Ref ID J:194249]

Nakagomi D; Suzuki K; Hosokawa J; Kobayashi Y; Suto A; Takatori H; Watanabe N; Matsue H; Murphy TL; Murphy KM; Shimada S; Nakajima H. 2013. Therapeutic potential of B and T lymphocyte attenuator expressed on CD8+ T cells for contact hypersensitivity. J Invest Dermatol 133(3):702-11. [PubMed: 23190882]  [MGI Ref ID J:196516]

Oya Y; Watanabe N; Kobayashi Y; Owada T; Oki M; Ikeda K; Suto A; Kagami S; Hirose K; Kishimoto T; Nakajima H. 2011. Lack of B and T lymphocyte attenuator exacerbates autoimmune disorders and induces Fas-independent liver injury in MRL-lpr/lpr mice. Int Immunol 23(5):335-44. [PubMed: 21521881]  [MGI Ref ID J:172190]

Sedy JR; Gavrieli M; Potter KG; Hurchla MA; Lindsley RC; Hildner K; Scheu S; Pfeffer K; Ware CF; Murphy TL; Murphy KM. 2005. B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. Nat Immunol 6(1):90-8. [PubMed: 15568026]  [MGI Ref ID J:94873]

Shubin NJ; Chung CS; Heffernan DS; Irwin LR; Monaghan SF; Ayala A. 2012. BTLA expression contributes to septic morbidity and mortality by inducing innate inflammatory cell dysfunction. J Leukoc Biol 92(3):593-603. [PubMed: 22459947]  [MGI Ref ID J:188094]

Shui JW; Larange A; Kim G; Vela JL; Zahner S; Cheroutre H; Kronenberg M. 2012. HVEM signalling at mucosal barriers provides host defence against pathogenic bacteria. Nature 488(7410):222-5. [PubMed: 22801499]  [MGI Ref ID J:186687]

Steinberg MW; Huang Y; Wang-Zhu Y; Ware CF; Cheroutre H; Kronenberg M. 2013. BTLA interaction with HVEM expressed on CD8(+) T cells promotes survival and memory generation in response to a bacterial infection. PLoS One 8(10):e77992. [PubMed: 24205057]  [MGI Ref ID J:209240]

Steinberg MW; Turovskaya O; Shaikh RB; Kim G; McCole DF; Pfeffer K; Murphy KM; Ware CF; Kronenberg M. 2008. A crucial role for HVEM and BTLA in preventing intestinal inflammation. J Exp Med 205(6):1463-76. [PubMed: 18519647]  [MGI Ref ID J:137040]

Tao R; Wang L; Han R; Wang T; Ye Q; Honjo T; Murphy TL; Murphy KM; Hancock WW. 2005. Differential effects of B and T lymphocyte attenuator and programmed death-1 on acceptance of partially versus fully MHC-mismatched cardiac allografts. J Immunol 175(9):5774-82. [PubMed: 16237069]  [MGI Ref ID J:119356]

Tao R; Wang L; Murphy KM; Fraser CC; Hancock WW. 2008. Regulatory T cell expression of herpesvirus entry mediator suppresses the function of B and T lymphocyte attenuator-positive effector T cells. J Immunol 180(10):6649-55. [PubMed: 18453584]  [MGI Ref ID J:134956]

Thangavelu G; Gill RG; Boon L; Ellestad KK; Anderson CC. 2013. Control of in vivo collateral damage generated by T cell immunity. J Immunol 191(4):1686-91. [PubMed: 23851694]  [MGI Ref ID J:205689]

Watanabe N; Gavrieli M; Sedy JR; Yang J; Fallarino F; Loftin SK; Hurchla MA; Zimmerman N; Sim J; Zang X; Murphy TL; Russell JH; Allison JP; Murphy KM. 2003. BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nat Immunol 4(7):670-9. [PubMed: 12796776]  [MGI Ref ID J:84084]

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 & HusbandryWhen 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* $3300.00
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.

Standard Supply

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

Supply Notes

  • 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* $4290.00
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.

Standard Supply

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

Supply Notes

  • 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
   000651 BALB/cJ
 
  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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