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 F3pN1 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. As expected, most splenic B cells express the 3-83 idiotype, but total B cell number may be lower than wild-type. The 3-83 antibody is non-autoreactive on the H-2^d background, while it is autoreactive on the H-2^b and H-2^k backgrounds. Mice heterozygous for both mutations and/or the H-2^b and H-2^k backgrounds exhibit an increase in frequency and absolute number of lambda-expressing B lymphocytes and a decrease in the expression of the 3-83 idiotype due to Igk RS recombination and Vl to Jl rearrangements. The 3-83KiJk<-> allele lacks endogenous Jk segments, preventing secondary Vk to Jk rearrangements. Mice homozygous for both mutations on the H-2^d, but not H-2^b and H-2^k backgrounds, do not retain 3-83 expression and do not have Vk to Jk recombination events. This strain generates an almost monoclonal B cell population. This mutant mouse strain may be useful in studies of B cell development, receptor editing, tolerance and antibody diversification.

Development
The targeting at the Igh locus was performed to replace the DNA region from upstream of DQ52 to downstream of JH4 with a vector that contains a loxP-flanked neo cassette, followed by the Ig 3-83 heavy chain gene, which includes its promoter region and the rearranged VDJ (with JH1). The construct was electroporated into 129P2/OlaHsd-derived E14.1TG3B1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The neomycin cassette was removed by transient transfection with a Cre recombinase expressing plasmid leaving a single loxP site. The resulting chimeric animals were crossed to C57BL/6 mice.

The targeting at the Igk locus was performed to replace the DNA region from upstream of Jk1 to downstream of Jk5 with a vector that contains a loxP-flanked neo cassette, followed by the Ig 3-83 light (kappa-k) chain gene, which includes its promoter region and the rearranged VJ (with Jk2), removing all endogenous Jk segments and preventing secondary Vk-Jk rearrangements. The construct was electroporated into 129P2/OlaHsd-derived E14.1TG3B1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The neomycin cassette was removed by transient transfection with a Cre recombinase expressing plasmid leaving a single loxP site 5' to the Vk gene. The resulting chimeric animals were crossed to C57BL/6 mice. Mice carrying the two mutations were bred together and then backcrossed to BALB/c (H2^d) for 10 generations.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Igh^tm2Rsky allele

011074

C.129P2(B6)-Igktm1Rsky Ightm2Rsky/PldJ

View Strains carrying   Igh^tm2Rsky     (1 strain)

Strains carrying other alleles of Igh

012642	B6.129P2(C)-Ightm2Cgn/J
007776	B6.129P2-Ightm2Mnz/J
007594	B6.129P2-Ptrpca Ightm1Mnz/J
001317	B6.Cg-Igha Thy1a Gpi1a/J
008332	C.129S1-Ightm1(Myc)Janz/J
001109	C.AL-Igho/SmnJ
001107	C.BKa-Ighb/IcrSmnJ
004126	C.Cg-Cd19tm1(cre)Cgn Ighb/J
007775	CBy.129P2(B6)-Ightm1Mnz/J

View Strains carrying other alleles of Igh     (9 strains)

Strains carrying other alleles of Igk

011074	C.129P2(B6)-Igktm1Rsky Ightm2Rsky/PldJ
008720	STOCK Tg(Igk*A)A02Dgs/J
008722	STOCK Tg(Igk*C)C06Dgs/J
008719	STOCK Tg(Igk*G)G07Dgs/J
008721	STOCK Tg(Igk*T)T04Dgs/J

View Strains carrying other alleles of Igk     (5 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Igh^tm2Rsky/Igh⁺ Igk^tm2Rsky/Igk⁺

        either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * BALB/c)

• immune system phenotype
• abnormal B cell differentiation
  • lack 3-83Ig+ mature B cells, although on an H2^d background some 3-83Ig+ immature B cells are detected in the bone marrow   (MGI Ref ID J:111431)
• hematopoietic system phenotype
• abnormal B cell differentiation
  • lack 3-83Ig+ mature B cells, although on an H2^d background some 3-83Ig+ immature B cells are detected in the bone marrow   (MGI Ref ID J:111431)
• cellular phenotype
• abnormal B cell differentiation
  • lack 3-83Ig+ mature B cells, although on an H2^d background some 3-83Ig+ immature B cells are detected in the bone marrow   (MGI Ref ID J:111431)

View Research Applications

Research Applications

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

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ightm2Rsky
Allele Name		targeted mutation 2, Klaus Rajewsky
Allele Type		Targeted (knock-in)
Common Name(s)		3-83Hi; 3-83mCkappa; Ightm1Pld;
Strain of Origin		129P2/OlaHsd
Promoter		Igh, immunoglobulin heavy chain complex, mouse, laboratory
Molecular Note		The rearranged 3-83 heavy chain was inserted into the IgHa locus via homologous recombination. A floxed neo selection cassette was also introduced and subsequently removed by Cre mediated recombination. [MGI Ref ID J:111431]
Allele Symbol		Igktm2Rsky
Allele Name		targeted mutation 2, Klaus Rajewsky
Allele Type		Targeted (knock-in)
Common Name(s)		3-83kappaiJkappa-; Igktm2Pld;
Promoter		Igk, immunoglobulin kappa chain complex, mouse, laboratory
Molecular Note		A targeting vector was used to insert a recombined Vk3-83-Jk5 region where all endogenous Jkappa segments are deleted. [MGI Ref ID J:111431]

Genotyping

Genotyping Information

Genotyping Protocols

Igh^tm2Rsky, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Pelanda R; Schwers S; Sonoda E; Torres RM; Nemazee D; Rajewsky K. 1997. Receptor editing in a transgenic mouse model: site, efficiency, and role in B cell tolerance and antibody diversification. Immunity 7(6):765-75. [PubMed: 9430222]  [MGI Ref ID J:111431]

Additional References

Igh^tm2Rsky related

Braun U; Rajewsky K; Pelanda R. 2000. Different sensitivity to receptor editing of B cells from mice hemizygous or homozygous for targeted Ig transgenes. Proc Natl Acad Sci U S A 97(13):7429-34. [PubMed: 10829061]  [MGI Ref ID J:63075]

Edry E; Azulay-Debby H; Melamed D. 2008. TOLL-like receptor ligands stimulate aberrant class switch recombination in early B cell precursors. Int Immunol 20(12):1575-85. [PubMed: 18974086]  [MGI Ref ID J:143931]

Eschbach C; Bach MP; Fidler I; Pelanda R; Kohler F; Rajewsky K; Jumaa H. 2011. Efficient generation of B lymphocytes by recognition of self-antigens. Eur J Immunol 41(8):2397-403. [PubMed: 21604259]  [MGI Ref ID J:176828]

Fraenkel S; Mostoslavsky R; Novobrantseva TI; Pelanda R; Chaudhuri J; Esposito G; Jung S; Alt FW; Rajewsky K; Cedar H; Bergman Y. 2007. Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin kappa-chain locus. Nat Immunol 8(7):715-22. [PubMed: 17546032]  [MGI Ref ID J:123344]

Liu S; Velez MG; Humann J; Rowland S; Conrad FJ; Halverson R; Torres RM; Pelanda R. 2005. Receptor editing can lead to allelic inclusion and development of B cells that retain antibodies reacting with high avidity autoantigens. J Immunol 175(8):5067-76. [PubMed: 16210610]  [MGI Ref ID J:119408]

Novobrantseva T; Xu S; Tan JE; Maruyama M; Schwers S; Pelanda R; Lam KP. 2005. Stochastic pairing of Ig heavy and light chains frequently generates B cell antigen receptors that are subject to editing in vivo. Int Immunol 17(4):343-50. [PubMed: 15710909]  [MGI Ref ID J:133067]

Rowland SL; DePersis CL; Torres RM; Pelanda R. 2010. Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation. J Exp Med 207(3):607-21. [PubMed: 20176802]  [MGI Ref ID J:158819]

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]

Igk^tm2Rsky related

Braun U; Rajewsky K; Pelanda R. 2000. Different sensitivity to receptor editing of B cells from mice hemizygous or homozygous for targeted Ig transgenes. Proc Natl Acad Sci U S A 97(13):7429-34. [PubMed: 10829061]  [MGI Ref ID J:63075]

Callen E; Jankovic M; Wong N; Zha S; Chen HT; Difilippantonio S; Di Virgilio M; Heidkamp G; Alt FW; Nussenzweig A; Nussenzweig M. 2009. Essential role for DNA-PKcs in DNA double-strand break repair and apoptosis in ATM-deficient lymphocytes. Mol Cell 34(3):285-97. [PubMed: 19450527]  [MGI Ref ID J:150435]

Casellas R; Nussenzweig A; Wuerffel R; Pelanda R; Reichlin A; Suh H; Qin XF; Besmer E; Kenter A; Rajewsky K; Nussenzweig MC. 1998. Ku80 is required for immunoglobulin isotype switching. EMBO J 17(8):2404-11. [PubMed: 9545251]  [MGI Ref ID J:127088]

Franco S; Murphy MM; Li G; Borjeson T; Boboila C; Alt FW. 2008. DNA-PKcs and Artemis function in the end-joining phase of immunoglobulin heavy chain class switch recombination. J Exp Med 205(3):557-64. [PubMed: 18316419]  [MGI Ref ID J:133132]

Rowland SL; DePersis CL; Torres RM; Pelanda R. 2010. Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation. J Exp Med 207(3):607-21. [PubMed: 20176802]  [MGI Ref ID J:158819]

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]

Zha S; Guo C; Boboila C; Oksenych V; Cheng HL; Zhang Y; Wesemann DR; Yuen G; Patel H; Goff PH; Dubois RL; Alt FW. 2011. ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks. Nature 469(7329):250-4. [PubMed: 21160472]  [MGI Ref ID J:167995]

Health & husbandry

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

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Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000651 BALB/cJ
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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