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. Species laboratory mouse Generation ?+F2pN1 Generation Definitions   Donating Investigator Klaus Rajewsky,   Max-Delbruck-Ctr. for Molecular 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 or protein) is detected by RT-PCR or FACS analysis of spleen tissue and cells, respectively. Homozygotes have reduced numbers of mature recirculating bone marrow and splenic B cells. B cell development is arrested between the transitional IgM+ (T1 + T2) and IgM^low (T3) stages. Homozygotes exhibit diminished antigen-specific antibody responses with decreased levels of IgM, IgG1, IgG2, IgG2b and IgG3. This mutant mouse strain may be useful in studies of B cell development and differentiation.

Development
A targeting vector was used to insert loxP sites on either side of exons 3 and 4, and a FRT site flanked neomycin resistance cassette. The construct was electroporated into C57BL/6-derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c recipient blastocysts. The donating investigator reported that all mice were maintained on a pure C57BL/6 background (see SNP note below). The resulting chimeric animals were crossed to C57BL/6 transgenic mice expressing Cre recombinase under the control of the cytomegalovirus promoter, to remove the floxed exons. The donating investigator reports that the mice do not carry the cre transgene.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Tnfrsf13c

000647

A/WySnJ

View Strains carrying other alleles of Tnfrsf13c     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Immunodeficiency, Common Variable, 2; CVID2   (TNFRSF13C) Immunodeficiency, Common Variable, 4; CVID4   (TNFRSF13C)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tnfrsf13c^tm1Mass/Tnfrsf13c^tm1Mass

        C57BL/6-Tnfrsf13c^tm1Mass

• hematopoietic system phenotype
• arrested B cell differentiation
  • a block in B cell development from IgM⁺ (T1 + T2) to IgM^low (T3) cells is seen   (MGI Ref ID J:92732)
• decreased mature B cell number
  • the number of mature recirculating B cells is reduced with about a 10-fold reduction in IgD⁺ B cells in the bone marrow and a 20-fold decrease in IgM^lowIgD⁺ B cells in the lymph nodes   (MGI Ref ID J:92732)
• • absent marginal zone B cells   (MGI Ref ID J:92732)
  • decreased B-2 B cell number
    • a reduction in peritoneal B2 cells but not B1 cells is seen   (MGI Ref ID J:92732)
• immune system phenotype
• abnormal B cell physiology
  • there is about a third reduction in the number of B cells that survive 36 hours of in vitro culturing compared to controls   (MGI Ref ID J:113556)
  • addition of Tnfsf13b (BAFF) to the culture does not elevate survival   (MGI Ref ID J:113556)
• • decreased IgG level
    • the titers of IgG1, IgG2a, IgG2b, and IgG3 are reduced   (MGI Ref ID J:92732)
  • • decreased IgG1 level
      • immunization with NP-CG produces a significantly smaller increase in IgG1 titers in mutants compared to wild-type mice and no secondary NP-specific response is detected in mutants   (MGI Ref ID J:92732)
    • decreased IgG2a level   (MGI Ref ID J:92732)
    • decreased IgG2b level   (MGI Ref ID J:92732)
    • decreased IgG3 level
      • immunization with NP-Ficoll produces a smaller increase in IgG3 titers in mutants compared to wild-type mice   (MGI Ref ID J:92732)
  • decreased IgM level
    • the titer of IgM but not IgA is reduced compared to wild-type mice   (MGI Ref ID J:92732)
    • immunization with NP-Ficoll produces a smaller increase in IgM titers in mutants compared to wild-type mice   (MGI Ref ID J:92732)
• arrested B cell differentiation
  • a block in B cell development from IgM⁺ (T1 + T2) to IgM^low (T3) cells is seen   (MGI Ref ID J:92732)
• decreased mature B cell number
  • the number of mature recirculating B cells is reduced with about a 10-fold reduction in IgD⁺ B cells in the bone marrow and a 20-fold decrease in IgM^lowIgD⁺ B cells in the lymph nodes   (MGI Ref ID J:92732)
• • absent marginal zone B cells   (MGI Ref ID J:92732)
  • decreased B-2 B cell number
    • a reduction in peritoneal B2 cells but not B1 cells is seen   (MGI Ref ID J:92732)
• cellular phenotype
• arrested B cell differentiation
  • a block in B cell development from IgM⁺ (T1 + T2) to IgM^low (T3) cells is seen   (MGI Ref ID J:92732)

Tnfrsf13c^tm1Mass/Tnfrsf13c^tm1Mass

        involves: C57BL/6

• immune system phenotype
• decreased lymphocyte cell number   (MGI Ref ID J:139293)
• • decreased mature B cell number   (MGI Ref ID J:139293)
• hematopoietic system phenotype
• decreased lymphocyte cell number   (MGI Ref ID J:139293)
• • decreased mature B cell number   (MGI Ref ID J:139293)

View Research Applications

Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      B cell deficiency

Research Tools
Immunology and Inflammation Research
      B cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tnfrsf13ctm1Mass
Allele Name		targeted mutation 1, Marc Schmidt-Supprian
Allele Type		Targeted (knock-out)
Common Name(s)		Baff-r-;
Mutation Made By		Klaus Rajewsky,   Max-Delbruck-Ctr. for Molecular Medicine
Strain of Origin		B6.Cg-Thy1
ES Cell Line Name		Bruce 4
ES Cell Line Strain		B6.Cg-Thy1
Gene Symbol and Name		Tnfrsf13c, tumor necrosis factor receptor superfamily, member 13c
Chromosome		15
Gene Common Name(s)		2010006P15Rik; B-cell maturation defect 1; BAFF-R; BAFFR; BROMIX; Bcmd-1; Bcmd1; CD268; CVID4; Lvis22; RGD1560810; RIKEN cDNA 2010006P15 gene; prolixin;
Molecular Note		Cre-recombinase excised a floxed region containing exons 3 and 4. The excised region encoded the entire extracellular and transmembrane domains and part of the cytoplasmic domain. RT-PCR did not detect mRNA in mutants. FACS analysis showed no surface expression of mutant splenic cells. [MGI Ref ID J:92732]

Genotyping

Genotyping Information

Genotyping Protocols

Tnfrsf13c^tm1Mass, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Sasaki Y; Casola S; Kutok JL; Rajewsky K; Schmidt-Supprian M. 2004. TNF family member B cell-activating factor (BAFF) receptor-dependent and -independent roles for BAFF in B cell physiology. J Immunol 173(4):2245-52. [PubMed: 15294936]  [MGI Ref ID J:92732]

Additional References

Tnfrsf13c^tm1Mass related

Enzler T; Bonizzi G; Silverman GJ; Otero DC; Widhopf GF; Anzelon-Mills A; Rickert RC; Karin M. 2006. Alternative and classical NF-kappa B signaling retain autoreactive B cells in the splenic marginal zone and result in lupus-like disease. Immunity 25(3):403-15. [PubMed: 16973390]  [MGI Ref ID J:113556]

Gardam S; Sierro F; Basten A; Mackay F; Brink R. 2008. TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals delivered to B cells by the BAFF receptor. Immunity 28(3):391-401. [PubMed: 18313334]  [MGI Ref ID J:132877]

Gardam S; Turner VM; Anderton H; Limaye S; Basten A; Koentgen F; Vaux DL; Silke J; Brink R. 2011. Deletion of cIAP1 and cIAP2 in murine B lymphocytes constitutively activates cell survival pathways and inactivates the germinal center response. Blood 117(15):4041-51. [PubMed: 21300983]  [MGI Ref ID J:172843]

Keren Z; Averbuch D; Shahaf G; Zisman-Rozen S; Golan K; Itkin T; Lapidot T; Mehr R; Melamed D. 2011. Chronic B cell deficiency from birth prevents age-related alterations in the B lineage. J Immunol 187(5):2140-7. [PubMed: 21810615]  [MGI Ref ID J:179123]

Mayne CG; Nashold FE; Sasaki Y; Hayes CE. 2009. Altered BAFF-receptor signaling and additional modifier loci contribute to systemic autoimmunity in A/WySnJ mice. Eur J Immunol 39(2):589-99. [PubMed: 19152335]  [MGI Ref ID J:144490]

Otipoby KL; Sasaki Y; Schmidt-Supprian M; Patke A; Gareus R; Pasparakis M; Tarakhovsky A; Rajewsky K. 2008. BAFF activates Akt and Erk through BAFF-R in an IKK1-dependent manner in primary mouse B cells. Proc Natl Acad Sci U S A 105(34):12435-8. [PubMed: 18713867]  [MGI Ref ID J:138966]

Rowland SL; Leahy KF; Halverson R; Torres RM; Pelanda R. 2010. BAFF receptor signaling aids the differentiation of immature B cells into transitional B cells following tonic BCR signaling. J Immunol 185(8):4570-81. [PubMed: 20861359]  [MGI Ref ID J:164719]

Sasaki Y; Calado DP; Derudder E; Zhang B; Shimizu Y; Mackay F; Nishikawa S; Rajewsky K; Schmidt-Supprian M. 2008. NIK overexpression amplifies, whereas ablation of its TRAF3-binding domain replaces BAFF:BAFF-R-mediated survival signals in B cells. Proc Natl Acad Sci U S A 105(31):10883-8. [PubMed: 18663224]  [MGI Ref ID J:139293]

Sasaki Y; Derudder E; Hobeika E; Pelanda R; Reth M; Rajewsky K; Schmidt-Supprian M. 2006. Canonical NF-kappaB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation. Immunity 24(6):729-39. [PubMed: 16782029]  [MGI Ref ID J:113365]

Scapini P; Hu Y; Chu CL; Migone TS; Defranco AL; Cassatella MA; Lowell CA. 2010. Myeloid cells, BAFF, and IFN-gamma establish an inflammatory loop that exacerbates autoimmunity in Lyn-deficient mice. J Exp Med 207(8):1757-73. [PubMed: 20624892]  [MGI Ref ID J:163472]

Waisman A; Kraus M; Seagal J; Ghosh S; Melamed D; Song J; Sasaki Y; Classen S; Lutz C; Brombacher F; Nitschke L; Rajewsky K. 2007. IgG1 B cell receptor signaling is inhibited by CD22 and promotes the development of B cells whose survival is less dependent on Ig alpha/beta. J Exp Med 204(4):747-58. [PubMed: 17420268]  [MGI Ref ID J:125719]

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, these mice may be bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

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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