Strain Name:

B6.Cg-Tg(LCK-NFKBIA)5Dwb/J

Stock Number:

003567

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Availability:

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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

Former Names C57BL/6-Tg(LCK-NFKBIA)5Dwb/J    (Changed: 24-FEB-11 )
Type Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating Investigator IMR Colony,   The Jackson Laboratory

Description
Mice hemizygous for TgN(LCK-NFKBIA)5Dwb transgene exhibit a complete inactivation of the NFKB signalling pathway. The T cell lineage expresses a trans-dominant form of IkBa that constitutively represses the activity of multiple NFKB/Rel proteins. Transgenic cells expressing this inhibitor exhibit a significant proliferative defect. Mitogenic stimulation of splenocytes leads to increased apoptosis of transgenic T cells. Transgene expression also impairs the development of normal T cell populations as evidenced by diminished numbers of TCRhiCD8 single-positive thymocytes. This defect is significantlly amplified in the periphery and is accompanied by a decrease in CD4+ T cells.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(LCK-NFKBIA)5Dwb allele
003330   B6;D2-Tg(LCK-NFKBIA)5Dwb/J
View Strains carrying   Tg(LCK-NFKBIA)5Dwb     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Ectodermal Dysplasia, Anhidrotic, with T-Cell Immunodeficiency, Autosomal Dominant   (NFKBIA)
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.

Tg(LCK-NFKBIA)5Dwb/0

        involves: C57BL/6 * DBA/2
  • immune system phenotype
  • abnormal CD8-positive, alpha-beta T cell differentiation
    • numbers of CD8 single-positive thymocytes bearing high levels of TCR are reduced by 40% compared to controls   (MGI Ref ID J:93003)
  • decreased CD4-positive, alpha beta T cell number
    • CD4+ T cell numbers are reduced in the spleen, lymph nodes, and blood though not to the degree of reduction observed for CD8+ T cells   (MGI Ref ID J:93003)
  • decreased CD8-positive, alpha-beta T cell number
    • CD8+ T cell numbers are reduced by two-thirds or more in the spleen, lymph nodes, and blood   (MGI Ref ID J:93003)
  • decreased T cell proliferation
    • thymocyotes only have one third the proliferation rate as controls when stimulated with PMA and ionomycin   (MGI Ref ID J:93003)
    • thymocyte proliferation is also severely curtailed in response to other mitogens   (MGI Ref ID J:93003)
    • addition of IL-2 to culture does not rescue the proliferation defect   (MGI Ref ID J:93003)
    • similar results were observed for B cell-depleted splenocytes   (MGI Ref ID J:93003)
  • decreased interleukin-2 secretion
    • thymocytes produce about 20-fold less IL-2 when stimulated compared to wild-type controls   (MGI Ref ID J:93003)
    • likewise, splenocytes only produce 8% the IL-2 as controls when stimulated   (MGI Ref ID J:93003)
  • increased T cell apoptosis
    • about twice the percentage of T cells are apoptotic after in vitro stimulation with Con-A   (MGI Ref ID J:93003)
    • this is observed for both CD4+ and CD8+ T cells   (MGI Ref ID J:93003)
    • anti-TCR stimulation produces similar results with more enhanced apoptosis observed for CD8+ T cells   (MGI Ref ID J:93003)
  • hematopoietic system phenotype
  • abnormal CD8-positive, alpha-beta T cell differentiation
    • numbers of CD8 single-positive thymocytes bearing high levels of TCR are reduced by 40% compared to controls   (MGI Ref ID J:93003)
  • decreased CD4-positive, alpha beta T cell number
    • CD4+ T cell numbers are reduced in the spleen, lymph nodes, and blood though not to the degree of reduction observed for CD8+ T cells   (MGI Ref ID J:93003)
  • decreased CD8-positive, alpha-beta T cell number
    • CD8+ T cell numbers are reduced by two-thirds or more in the spleen, lymph nodes, and blood   (MGI Ref ID J:93003)
  • decreased T cell proliferation
    • thymocyotes only have one third the proliferation rate as controls when stimulated with PMA and ionomycin   (MGI Ref ID J:93003)
    • thymocyte proliferation is also severely curtailed in response to other mitogens   (MGI Ref ID J:93003)
    • addition of IL-2 to culture does not rescue the proliferation defect   (MGI Ref ID J:93003)
    • similar results were observed for B cell-depleted splenocytes   (MGI Ref ID J:93003)
  • increased T cell apoptosis
    • about twice the percentage of T cells are apoptotic after in vitro stimulation with Con-A   (MGI Ref ID J:93003)
    • this is observed for both CD4+ and CD8+ T cells   (MGI Ref ID J:93003)
    • anti-TCR stimulation produces similar results with more enhanced apoptosis observed for CD8+ T cells   (MGI Ref ID J:93003)
  • cellular phenotype
  • increased T cell apoptosis
    • about twice the percentage of T cells are apoptotic after in vitro stimulation with Con-A   (MGI Ref ID J:93003)
    • this is observed for both CD4+ and CD8+ T cells   (MGI Ref ID J:93003)
    • anti-TCR stimulation produces similar results with more enhanced apoptosis observed for CD8+ T cells   (MGI Ref ID J:93003)

Tg(LCK-NFKBIA)5Dwb/?

        involves: BALB/c * C57BL/6 * DBA/2
  • immune system phenotype
  • abnormal T-helper 1 physiology
    • the decreased delayed type hypersensitivity response to antigen rechallenge and the decreased IFN-gamma secretion by T cells isolated from the draining lymph nodes to these rechallenged areas demonstrate a defective Th1 response   (MGI Ref ID J:145531)
    • defective class switching of antigen-specific immunoglobulin to IgG2a gives further evidence of a defective Th1-response   (MGI Ref ID J:145531)
  • decreased interferon-gamma secretion
    • T cells isolated from the draining lymph nodes of mice rechallenged with antigen produce significantly less IFN-gamma than controls   (MGI Ref ID J:145531)
  • decreased susceptibility to type I hypersensitivity reaction
    • antigen rechallenge in the lung leads to slightly less periarterial inflammation than in controls   (MGI Ref ID J:145531)
    • there is significant attenuation of airway hyperresponsiveness in these mice upon antigen rechallenge in the lung   (MGI Ref ID J:145531)
    • the number of cells isolated from BAL fluid in these aerosol rechallenged mice is one-third of controls   (MGI Ref ID J:145531)
    • the level of antigen-specific IgG2a in aerosol sensitized mice is markedly reduced   (MGI Ref ID J:145531)
  • decreased susceptibility to type IV hypersensitivity reaction
    • antigenic challenge after prior sensitization leads to 4-fold less swelling in the footpads compared to controls   (MGI Ref ID J:145531)
  • hematopoietic system phenotype
  • abnormal T-helper 1 physiology
    • the decreased delayed type hypersensitivity response to antigen rechallenge and the decreased IFN-gamma secretion by T cells isolated from the draining lymph nodes to these rechallenged areas demonstrate a defective Th1 response   (MGI Ref ID J:145531)
    • defective class switching of antigen-specific immunoglobulin to IgG2a gives further evidence of a defective Th1-response   (MGI Ref ID J:145531)
View Research Applications

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

Cell Biology Research
Genes Regulating Growth and Proliferation

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
Intracellular Signaling Molecules

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(LCK-NFKBIA)5Dwb
Allele Name transgene insertion 5, Dean W Ballard
Allele Type Transgenic (Dominant negative, Inserted expressed sequence)
Common Name(s) IkappaBalpha(deltaN); IkappaNalphadeltaN-Tg; LCK;
Mutation Made ByDr. Dean Ballard,   Vanderbilt University School of Medicine
Strain of OriginC57BL/6 x DBA/2
Expressed Gene NFKBIA, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, human
Promoter LCK, LCK proto-oncogene, Src family tyrosine kinase, human
Molecular Note An amino acid-truncated human NFKBIA gene (coding for amino acids 37-317) fused to a FLAG epitope was placed under the control of a human LCK promoter. The protein encoded by this transgene lacks sequences required for signal-dependent degradation and functions as a constitutive repressor of multiple NK-kappaB pathways. Transgene expression was readily detected in the thymus and spleen as determined by immunoblot analysis. [MGI Ref ID J:93003]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(LCK-NFKBIA)5Dwb, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Boothby MR; Mora AL; Scherer DC; Brockman JA; Ballard DW. 1997. Perturbation of the T lymphocyte lineage in transgenic mice expressing a constitutive repressor of nuclear factor (NF)-kappaB. J Exp Med 185(11):1897-907. [PubMed: 9166419]  [MGI Ref ID J:93003]

Additional References

Tg(LCK-NFKBIA)5Dwb related

Aronica MA; Mora AL; Mitchell DB; Finn PW; Johnson JE; Sheller JR; Boothby MR. 1999. Preferential role for NF-kappa B/Rel signaling in the type 1 but not type 2 T cell-dependent immune response in vivo. J Immunol 163(9):5116-24. [PubMed: 10528218]  [MGI Ref ID J:145531]

Bezbradica JS; Hill T; Stanic AK; Van Kaer L; Joyce S. 2005. Commitment toward the natural T (iNKT) cell lineage occurs at the CD4+8+ stage of thymic ontogeny. Proc Natl Acad Sci U S A 102(14):5114-9. [PubMed: 15792999]  [MGI Ref ID J:97416]

Corn RA; Aronica MA; Zhang F; Tong Y; Stanley SA; Kim SR; Stephenson L; Enerson B; McCarthy S; Mora A; Boothby M. 2003. T cell-intrinsic requirement for NF-kappaB induction in postdifferentiation IFN-gamma production and clonal expansion in a Th1 response. J Immunol 171(4):1816-24. [PubMed: 12902482]  [MGI Ref ID J:84809]

Corn RA; Hunter C; Liou HC; Siebenlist U; Boothby MR. 2005. Opposing roles for RelB and Bcl-3 in regulation of T-box expressed in T cells, GATA-3, and Th effector differentiation. J Immunol 175(4):2102-10. [PubMed: 16081776]  [MGI Ref ID J:107516]

Jones RG; Saibil SD; Pun JM; Elford AR; Bonnard M; Pellegrini M; Arya S; Parsons ME; Krawczyk CM; Gerondakis S; Yeh WC; Woodgett JR; Boothby MR; Ohashi PS. 2005. NF-kappaB couples protein kinase B/Akt signaling to distinct survival pathways and the regulation of lymphocyte homeostasis in vivo. J Immunol 175(6):3790-9. [PubMed: 16148125]  [MGI Ref ID J:116725]

Lee AJ; Wu X; Cheng H; Zhou X; Cheng X; Sun SC. 2010. CARMA1 regulation of regulatory T cell development involves modulation of interleukin-2 receptor signaling. J Biol Chem 285(21):15696-703. [PubMed: 20233721]  [MGI Ref ID J:163899]

Lee AJ; Zhou X; Chang M; Hunzeker J; Bonneau RH; Zhou D; Sun SC. 2010. Regulation of natural killer T-cell development by deubiquitinase CYLD. EMBO J 29(9):1600-12. [PubMed: 20224552]  [MGI Ref ID J:160381]

Molinero LL; Cubre A; Mora-Solano C; Wang Y; Alegre ML. 2012. T cell receptor/CARMA1/NF-kappaB signaling controls T-helper (Th) 17 differentiation. Proc Natl Acad Sci U S A 109(45):18529-34. [PubMed: 23091043]  [MGI Ref ID J:191230]

Molinero LL; Miller ML; Evaristo C; Alegre ML. 2011. High TCR stimuli prevent induced regulatory T cell differentiation in a NF-kappaB-dependent manner. J Immunol 186(8):4609-17. [PubMed: 21411734]  [MGI Ref ID J:172516]

Mora AL; Corn RA; Stanic AK; Goenka S; Aronica M; Stanley S; Ballard DW; Joyce S; Boothby M. 2003. Antiapoptotic function of NF-kappaB in T lymphocytes is influenced by their differentiation status: roles of Fas, c-FLIP, and Bcl-xL. Cell Death Differ 10(9):1032-44. [PubMed: 12934078]  [MGI Ref ID J:128143]

Mora AL; Stanley S; Armistead W; Chan AC; Boothby M. 2001. Inefficient ZAP-70 phosphorylation and decreased thymic selection in vivo result from inhibition of NF-kappaB/Rel. J Immunol 167(10):5628-35. [PubMed: 11698434]  [MGI Ref ID J:135121]

Zhou P; Balin SJ; Mashayekhi M; Hwang KW; Palucki DA; Alegre ML. 2005. Transplantation tolerance in NF-kappaB-impaired mice is not due to regulation but is prevented by transgenic expression of Bcl-xL. J Immunol 174(6):3447-53. [PubMed: 15749879]  [MGI Ref ID J:97694]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

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* $2140.00
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* $2782.00
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
   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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