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 Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N2 Generation Definitions   Donating Investigator Dr. Dean W. Ballard,   Vanderbilt University School of Medicine

Appearance
gray
Related Genotype: a/a Myo5a^d/Myo5a^d

black
Related Genotype: a/a

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 TCR ^hiCD8 single-positive thymocytes. This defect is significantly amplified in the periphery and is accompanied by a decrease in CD4 ⁺ T cells.

Control Information

	Control
	Noncarrier
Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(LCK-NFKBIA)5Dwb allele

003567

B6.Cg-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

Tg(LCK-NFKBIA)5Dwb/0

        involves: C57BL/6 * DBA/2

• immune system phenotype
• abnormal CD8-positive 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 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 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 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 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 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)
• cellular phenotype
• abnormal CD8-positive 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 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)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

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)

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 (random, expressed)
Common Name(s)		IkappaBalpha(deltaN); IkappaNalphadeltaN-Tg; LCK;
Mutation Made By		Dr. Dean Ballard,   Vanderbilt University School of Medicine
Strain of Origin		C57BL/6 x DBA/2
Expressed Gene		NFKBIA, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, human
Promoter		LCK, lymphocyte-specific protein 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.

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Noncarrier
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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