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. Species laboratory mouse   Donating Investigator Dr. 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

Relb^{Tg(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)

Relb^{Tg(H2-K1/GH1)106Bri}/Relb^{Tg(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 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)
• cellular phenotype
• decreased T cell proliferation   (MGI Ref ID J:76450)
• decreased pre-B cell number   (MGI Ref ID J:76450)

Relb^{Tg(H2-K1/GH1)106Bri}/Relb^{Tg(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 (random, gene disruption)
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 Origin		C57BL/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

Relb^{Tg(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]

Relb^{Tg(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]

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]

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 & Husbandry	When 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.
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
	Wild-type from the colony
	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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