Strain Name:

C57BL/6-RelbTg(H2-K1/GH1)106Bri/J

Stock Number:

002835

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Availability:

Cryopreserved - Ready for recovery

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(H2KhGH1)106Bri RelbTg106Bri/J    (Changed: 31-MAR-06 )
Type Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. David Lo,   Scripps Research Institute

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for this mutation are viable but not fertile. This mutation was caused by the chance integration of a class I MHC clone resulting in the disruption of Relb. Homozygous mutant mice display numerous immune system defects. There is a complete absence of lymphocytes in peripheral lymph nodes and Peyer's patches. The thymic medulla fails to form fully. Splenomegaly is observed along with and severe inflammatory syndrome with mixed granulocyte/monocyte infiltrates in lung, liver, and other tissues. A loss of dendritic cell function and regulation of chemokine expression by nonlymphoid cells (such as fibroblasts) is also observed. Symptoms become apparent at three weeks to several months after birth.

Development
Line 272-4 was generated by microinjection of a construct containing a 7.8 kb fragment containing the complete mouse H2-K<k> structural locus and 2 kb of 5' flanking sequence, as well as a nonfunctional 2.1 kb portion of the human growth hormone gene (hGH1), which serves as a marker gene. Transgene insertion interrupted the Relb locus, resulting in inactivation of Relb. Line 272-4 is referred to as Tg(H2-K + GH1)Bri106 in the primary reference.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Relb
012856   A;C-Relbshep/GrsrJ
View Strains carrying other alleles of Relb     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

RelbTg(H2-K1/GH1)106Bri/Relb+

        involves: C57BL/6
  • immune system phenotype
  • decreased NK T cell number
    • Valpha14i NKT cells are reduced in the thymus, spleen, liver, and bone marrow compared to in wild-type mice   (MGI Ref ID J:120659)
  • decreased Peyer's patch number   (MGI Ref ID J:120659)
  • small Peyer's patches   (MGI Ref ID J:120659)
  • hematopoietic system phenotype
  • decreased NK T cell number
    • Valpha14i NKT cells are reduced in the thymus, spleen, liver, and bone marrow compared to in wild-type mice   (MGI Ref ID J:120659)

RelbTg(H2-K1/GH1)106Bri/RelbTg(H2-K1/GH1)106Bri

        C57BL/6
  • mortality/aging
  • partial preweaning lethality
    • fewer than expected mice survived to weaning (12% compared to the expected 25%)   (MGI Ref ID J:76450)
  • premature death
    • mice that survive to weaning die within several months   (MGI Ref ID J:76450)
  • immune system phenotype
  • abnormal Peyer's patch morphology
    • Peyer's patch and lymph nodes are extremely difficult to find   (MGI Ref ID J:76450)
  • abnormal antigen presentation
    • antigen-presenting function is impaired   (MGI Ref ID J:23081)
  • abnormal lymph node morphology
    • Peyer's patch and lymph nodes are extremely difficult to find   (MGI Ref ID J:76450)
  • abnormal thymus medulla morphology
    • the medulla is almost completely absent   (MGI Ref ID J:76450)
    • the medulla is almost completely absent   (MGI Ref ID J:23081)
  • decreased B cell number   (MGI Ref ID J:76450)
    • decreased pre-B cell number   (MGI Ref ID J:76450)
  • decreased T cell number
    • 18% of spleen cells compared to 36% in wild-type mice   (MGI Ref ID J:76450)
    • however, the total number of T cells is normal   (MGI Ref ID J:76450)
  • decreased T cell proliferation   (MGI Ref ID J:76450)
  • enlarged spleen
    • spleen is enlarged (3- to 10-fold larger than in wild-type mice) and unusually firm   (MGI Ref ID J:76450)
  • increased granulocyte number   (MGI Ref ID J:23081)
    • 23% of total spleen compared to 0.5% in wild-type mice   (MGI Ref ID J:76450)
  • increased inflammatory response
    • inflammatory infiltrate is present in the epididymis, pancreas, skeletal muscle and cardiac muscle   (MGI Ref ID J:76450)
    • mice exhibit severe inflammatory syndrome with mixed granylocyte/monocyte infiltrate in the lung, liver and other tissues   (MGI Ref ID J:23081)
    • glomerulonephritis
      • in older mice   (MGI Ref ID J:76450)
    • liver inflammation   (MGI Ref ID J:76450)
    • lung inflammation
      • infiltrate accumulates in the lung without exudates or pneumonia   (MGI Ref ID J:76450)
    • skin inflammation
      • mice exhibit inflammation in the skin of the ear, tail and periorbital regions   (MGI Ref ID J:76450)
  • increased macrophage cell number   (MGI Ref ID J:23081)
    • 13% to 18% of total spleen compared to 3% to 5% in wild-type mice   (MGI Ref ID J:76450)
  • growth/size/body phenotype
  • decreased body size
    • at weaning mice are often smaller than wild-type mice   (MGI Ref ID J:76450)
    • cachexia
      • all mice that survive past weaning spontaneously develop wasting syndrome   (MGI Ref ID J:76450)
  • respiratory system phenotype
  • abnormal lung morphology
    • lungs are mottled   (MGI Ref ID J:76450)
  • lung inflammation
    • infiltrate accumulates in the lung without exudates or pneumonia   (MGI Ref ID J:76450)
  • liver/biliary system phenotype
  • liver fibrosis   (MGI Ref ID J:76450)
  • liver inflammation   (MGI Ref ID J:76450)
  • pale liver   (MGI Ref ID J:76450)
  • renal/urinary system phenotype
  • glomerulonephritis
    • in older mice   (MGI Ref ID J:76450)
  • homeostasis/metabolism phenotype
  • skin edema
    • skin on the tail and eyes becomes edematous   (MGI Ref ID J:76450)
  • hematopoietic system phenotype
  • abnormal thymus medulla morphology
    • the medulla is almost completely absent   (MGI Ref ID J:76450)
    • the medulla is almost completely absent   (MGI Ref ID J:23081)
  • decreased B cell number   (MGI Ref ID J:76450)
    • decreased pre-B cell number   (MGI Ref ID J:76450)
  • decreased T cell number
    • 18% of spleen cells compared to 36% in wild-type mice   (MGI Ref ID J:76450)
    • however, the total number of T cells is normal   (MGI Ref ID J:76450)
  • decreased T cell proliferation   (MGI Ref ID J:76450)
  • enlarged spleen
    • spleen is enlarged (3- to 10-fold larger than in wild-type mice) and unusually firm   (MGI Ref ID J:76450)
  • increased granulocyte number   (MGI Ref ID J:23081)
    • 23% of total spleen compared to 0.5% in wild-type mice   (MGI Ref ID J:76450)
  • increased macrophage cell number   (MGI Ref ID J:23081)
    • 13% to 18% of total spleen compared to 3% to 5% in wild-type mice   (MGI Ref ID J:76450)
  • integument phenotype
  • hyperkeratosis
    • in the skin of the ears   (MGI Ref ID J:76450)
  • ruffled hair
    • fur becomes ruffled   (MGI Ref ID J:76450)
  • skin edema
    • skin on the tail and eyes becomes edematous   (MGI Ref ID J:76450)
  • skin inflammation
    • mice exhibit inflammation in the skin of the ear, tail and periorbital regions   (MGI Ref ID J:76450)
  • endocrine/exocrine gland phenotype
  • abnormal thymus medulla morphology
    • the medulla is almost completely absent   (MGI Ref ID J:76450)
    • the medulla is almost completely absent   (MGI Ref ID J:23081)

RelbTg(H2-K1/GH1)106Bri/RelbTg(H2-K1/GH1)106Bri

        involves: C57BL/6
  • immune system phenotype
  • absent Peyer's patches   (MGI Ref ID J:120659)
  • absent lymph nodes   (MGI Ref ID J:120659)
  • decreased NK T cell number
    • Valpha14i NKT cells are reduced in the thymus, spleen, liver, and bone marrow compared to in wild-type mice   (MGI Ref ID J:120659)
  • decreased circulating interleukin-4 level
    • serum from alpha-GalCer-treated mice lacks IL4 unlike similarly treated wild-type mice   (MGI Ref ID J:120659)
  • increased inflammatory response
    • mice develop multi-organ inflammation unlike wild-type mice   (MGI Ref ID J:120659)
  • homeostasis/metabolism phenotype
  • decreased circulating interleukin-4 level
    • serum from alpha-GalCer-treated mice lacks IL4 unlike similarly treated wild-type mice   (MGI Ref ID J:120659)
  • hematopoietic system phenotype
  • decreased NK T cell number
    • Valpha14i NKT cells are reduced in the thymus, spleen, liver, and bone marrow compared to in wild-type mice   (MGI Ref ID J:120659)

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol RelbTg(H2-K1/GH1)106Bri
Allele Name transgene insertion 106, Ralph L Brinster
Allele Type Transgenic (Inserted expressed sequence, Null/Knockout)
Common Name(s) 272H; RelbTg(H2K/GH1)106Bri; RelbTg106Bri; Tg(H-2K + GH1); Tg(H-2K +GH1)Bri106; Tg(H2KhGH1)106Bri; line 272-4; relb-;
Strain of OriginC57BL/6
Gene Symbol and Name Relb, avian reticuloendotheliosis viral (v-rel) oncogene related B
Chromosome 7
Gene Common Name(s) I-REL; IREL; REL-B; shep; spontaneous hepatitis;
Molecular Note The mutation was generated by microinjection of a construct containing a 7.8 kb fragment that includes the complete mouse H2-K structural locus and 2 kb of 5' flanking sequence, as well as a nonfunctional 2.1 kb portion of the human growth hormone gene (hGH1), which serves as a marker gene. The random insertion of this transgene just downstream of the exon encoding the Rel domain disrupted the gene. RT-PCR analysis of RNA derived from slpeen and thymus of homozygous mice demonstrated that no detectable transcript was expressed from this allele. Immunohistochemistry experiments on sections of thymus and spleen of homozygous mice confirmed that no detectable encoded protein was present. [MGI Ref ID J:23081]

Genotyping

Genotyping Information

Genotyping Protocols

RelbTg(H2-K1/GH1)106Bri, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lo D; Quill H; Burkly L; Scott B; Palmiter RD; Brinster RL. 1992. A recessive defect in lymphocyte or granulocyte function caused by an integrated transgene. Am J Pathol 141(5):1237-46. [PubMed: 1443055]  [MGI Ref ID J:76450]

Additional References

Burkly L; Hession C; Ogata L; Reilly C; Marconi LA; Olson D; Tizard R; Cate R; Lo D. 1995. Expression of relB is required for the development of thymic medulla and dendritic cells. Nature 373(6514):531-6. [PubMed: 7845467]  [MGI Ref ID J:23081]

RelbTg(H2-K1/GH1)106Bri related

Akiyama T; Shimo Y; Yanai H; Qin J; Ohshima D; Maruyama Y; Asaumi Y; Kitazawa J; Takayanagi H; Penninger JM; Matsumoto M; Nitta T; Takahama Y; Inoue J. 2008. The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity 29(3):423-37. [PubMed: 18799149]  [MGI Ref ID J:139649]

Burkly L; Hession C; Ogata L; Reilly C; Marconi LA; Olson D; Tizard R; Cate R; Lo D. 1995. Expression of relB is required for the development of thymic medulla and dendritic cells. Nature 373(6514):531-6. [PubMed: 7845467]  [MGI Ref ID J:23081]

DeKoning J; DiMolfetto L; Reilly C; Wei Q; Havran WL; Lo D. 1997. Thymic cortical epithelium is sufficient for the development of mature T cells in relB-deficient mice. J Immunol 158(6):2558-66. [PubMed: 9058787]  [MGI Ref ID J:107546]

Elewaut D; Shaikh RB; Hammond KJ; De Winter H; Leishman AJ; Sidobre S; Turovskaya O; Prigozy TI; Ma L; Banks TA; Lo D; Ware CF; Cheroutre H; Kronenberg M. 2003. NIK-dependent RelB activation defines a unique signaling pathway for the development of V alpha 14i NKT cells. J Exp Med 197(12):1623-33. [PubMed: 12810685]  [MGI Ref ID J:120659]

Gray DH; Seach N; Ueno T; Milton MK; Liston A; Lew AM; Goodnow CC; Boyd RL. 2006. Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood 108(12):3777-85. [PubMed: 16896157]  [MGI Ref ID J:140442]

Guerin S; Baron ML; Valero R; Herrant M; Auberger P; Naquet P. 2002. RelB reduces thymocyte apoptosis and regulates terminal thymocyte maturation. Eur J Immunol 32(1):1-9. [PubMed: 11753998]  [MGI Ref ID J:73939]

Le Bon A; Montoya M; Edwards MJ; Thompson C; Burke SA; Ashton M; Lo D; Tough DF; Borrow P. 2006. A role for the transcription factor RelB in IFN-alpha production and in IFN-alpha-stimulated cross-priming. Eur J Immunol 36(8):2085-93. [PubMed: 16810633]  [MGI Ref ID J:115794]

Li J; Li Y; Yao JY; Jin R; Zhu MZ; Qian XP; Zhang J; Fu YX; Wu L; Zhang Y; Chen WF. 2007. Developmental pathway of CD4+CD8- medullary thymocytes during mouse ontogeny and its defect in Aire-/- mice. Proc Natl Acad Sci U S A 104(46):18175-80. [PubMed: 17984055]  [MGI Ref ID J:127244]

MacDonald KP; Kuns RD; Rowe V; Morris ES; Banovic T; Bofinger H; O'Sullivan B; Markey KA; Don AL; Thomas R; Hill GR. 2007. Effector and regulatory T-cell function is differentially regulated by RelB within antigen-presenting cells during GVHD. Blood 109(11):5049-57. [PubMed: 17327399]  [MGI Ref ID J:145428]

Martucci C; Franchi S; Lattuada D; Panerai AE; Sacerdote P. 2007. Differential involvement of RelB in morphine-induced modulation of chemotaxis, NO, and cytokine production in murine macrophages and lymphocytes. J Leukoc Biol 81(1):344-54. [PubMed: 17023558]  [MGI Ref ID J:117261]

Naspetti M; Aurrand-Lions M; DeKoning J; Malissen M; Galland F ; Lo D ; Naquet P. 1997. Thymocytes and RelB-dependent medullary epithelial cells provide growth-promoting and organization signals, respectively, to thymic medullary stromal cells. Eur J Immunol 27(6):1392-7. [PubMed: 9209490]  [MGI Ref ID J:40940]

O'Sullivan BJ; Pai S; Street S; An X; MacDonald KP; Wong M; Strutton G; Gerondakis S; Steptoe RJ; de St Groth BF; Hill GR; Thomas R. 2011. Immunotherapy with costimulatory dendritic cells to control autoimmune inflammation. J Immunol 187(8):4018-30. [PubMed: 21900177]  [MGI Ref ID J:179324]

Oldstone MB; Race R; Thomas D; Lewicki H; Homann D; Smelt S; Holz A; Koni P; Lo D; Chesebro B; Flavell R. 2002. Lymphotoxin-alpha- and lymphotoxin-beta-deficient mice differ in susceptibility to scrapie: evidence against dendritic cell involvement in neuroinvasion. J Virol 76(9):4357-63. [PubMed: 11932402]  [MGI Ref ID J:126282]

Qin J; Konno H; Ohshima D; Yanai H; Motegi H; Shimo Y; Hirota F; Matsumoto M; Takaki S; Inoue J; Akiyama T. 2007. Developmental stage-dependent collaboration between the TNF receptor-associated factor 6 and lymphotoxin pathways for B cell follicle organization in secondary lymphoid organs. J Immunol 179(10):6799-807. [PubMed: 17982070]  [MGI Ref ID J:153863]

Ripen AM; Nitta T; Murata S; Tanaka K; Takahama Y. 2011. Ontogeny of thymic cortical epithelial cells expressing the thymoproteasome subunit beta5t. Eur J Immunol 41(5):1278-87. [PubMed: 21469133]  [MGI Ref ID J:175402]

Tan JK; Ni K; Le F; O'Neill HC. 2007. Hematopoiesis of immature myeloid dendritic cells in stroma-dependent spleen long-term cultures occurs independently of NF-KB/RelB function. Exp Hematol 35(10):1580-93. [PubMed: 17889723]  [MGI Ref ID J:126347]

Wu L; D'Amico A; Winkel KD; Suter M; Lo D; Shortman K. 1998. RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. Immunity 9(6):839-47. [PubMed: 9881974]  [MGI Ref ID J:110512]

Xia Y; Chen S; Wang Y; Mackman N; Ku G; Lo D; Feng L. 1999. RelB modulation of IkappaBalpha stability as a mechanism of transcription suppression of interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in fibroblasts. Mol Cell Biol 19(11):7688-96. [PubMed: 10523657]  [MGI Ref ID J:119904]

Xiu Y; Xu H; Zhao C; Li J; Morita Y; Yao Z; Xing L; Boyce BF. 2014. Chloroquine reduces osteoclastogenesis in murine osteoporosis by preventing TRAF3 degradation. J Clin Invest 124(1):297-310. [PubMed: 24316970]  [MGI Ref ID J:207911]

Zhang H; Hilton MJ; Anolik JH; Welle SL; Zhao C; Yao Z; Li X; Wang Z; Boyce BF; Xing L. 2014. NOTCH inhibits osteoblast formation in inflammatory arthritis via noncanonical NF-kappaB. J Clin Invest 124(7):3200-14. [PubMed: 24892805]  [MGI Ref ID J:213803]

Zhao C; Xiu Y; Ashton J; Xing L; Morita Y; Jordan CT; Boyce BF. 2012. Noncanonical NF-kappaB signaling regulates hematopoietic stem cell self-renewal and microenvironment interactions. Stem Cells 30(4):709-18. [PubMed: 22290873]  [MGI Ref ID J:190505]

de Souza AR; Zago M; Eidelman DH; Hamid Q; Baglole CJ. 2014. Aryl hydrocarbon receptor (AhR) attenuation of subchronic cigarette smoke-induced pulmonary neutrophilia is associated with retention of nuclear RelB and suppression of intercellular adhesion molecule-1 (ICAM-1). Toxicol Sci 140(1):204-23. [PubMed: 24752502]  [MGI Ref ID J:212832]

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, hemizygous mice are bred together. Reproduction is good. The expected coat color from breeding is Black. Homozygous mice are viable but not fertile.

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.

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* $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.

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
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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