Description

Strain Information

Type Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   17-AUG-11 Species laboratory mouse Generation N10+F5 (15-FEB-13) Generation Definitions   Donating Investigator Klaus Rajewsky,   Max-Delbruck-Ctr. for Molecular Medicine

Description
These B1-8i mutant mice carry two copies of V_HD_HJ_H gene arrangements in their immunoglobulin heavy chain complex (IgH) alleles, representing a recombined antibody variable region derived from a 4-hydroxy-3-nitrophenylacetyl binding antibody (B1-8), replacing an endogenous IgH-D element (DQ52) and the IgH-J elements. A silent point mutation in codon 92 inactivates the internal heptameric recombination signal sequence (RSS), abolishing endogenous V_H replacement and increasing the stability of the gene segment. Mice homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This strain may be useful for studying the effect of a restricted antibody repertoire on immune responses.

Development
The B1-8VDJ targeting vector was designed to replace endogenous sequence encompassing a 3' Igh-D element (DQ52) and the Igh-J elements of immunoglobulin heavy chain complex (IgH) with a recombined antibody variable region derived from a 4-hydroxy-3-nitrophenyl acetyl binding antibody (B1-8). The B1-8 variable region was modified to contain a point mutation in codon 92, inactivating an internal heptameric recombination signal sequence. A loxP-flanked neomycin resistance (neo) cassette was inserted upstream of the B1-8 region. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a pIC-Cre expression plasmid to delete the floxed-neo cassette, and were injected into CB.20 (C57BL/6 congenic with BALB/c at the IgH locus) blastocysts. The donating investigator stated that the resulting chimeric mice were bred to CB.20 mice and offspring were backcrossed to CB.20 (see SNP note below) at least 10 generations to establish a colony of homozygous B1-8i mice. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

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, 4 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
	100903 B6129PF2/J	(approximate)
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Igh

007776	B6.129P2-Ightm2Mnz/J
007594	B6.129P2-Ptrpca Ightm1Mnz/J
001317	B6.Cg-Igha Thy1a Gpi1a/J
011074	C.129P2(B6)-Igktm1Rsky Ightm2Rsky/PldJ
012235	C.129P2(B6)-Igktm2Rsky Ightm2Rsky/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     (10 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^tm2Cgn/Igh⁺

        involves: 129P2/OlaHsd * BALB/c * C57BL/Ka

• immune system phenotype
• abnormal B cell differentiation
  • reduced number of CD43+ B cell progenitors; however, the overall number of splenic B cells is similar to wild-type   (MGI Ref ID J:79556)
• hematopoietic system phenotype
• abnormal B cell differentiation
  • reduced number of CD43+ B cell progenitors; however, the overall number of splenic B cells is similar to wild-type   (MGI Ref ID J:79556)
• cellular phenotype
• abnormal B cell differentiation
  • reduced number of CD43+ B cell progenitors; however, the overall number of splenic B cells is similar to wild-type   (MGI Ref ID J:79556)

Igh^tm2Cgn/Igh⁺

        involves: 129P2/OlaHsd * C57BL/6

• hematopoietic system phenotype
• abnormal immunoglobulin light chain V-J recombination
  • the percentage of B cells expressing lambda light chain is about 2 times higher than in wild-type mice   (MGI Ref ID J:144033)
• immune system phenotype
• abnormal immunoglobulin light chain V-J recombination
  • the percentage of B cells expressing lambda light chain is about 2 times higher than in wild-type mice   (MGI Ref ID J:144033)
• cellular phenotype
• abnormal immunoglobulin light chain V-J recombination
  • the percentage of B cells expressing lambda light chain is about 2 times higher than in wild-type mice   (MGI Ref ID J:144033)

View Research Applications

Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines
Immunodeficiency
      B cell defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ightm2Cgn
Allele Name		targeted mutation 2, University of Cologne
Allele Type		Targeted (knock-in)
Common Name(s)		B1-8i; B18; IgH, B1-8-HC; IghB1-8; VHEmua;
Mutation Made By		Klaus Rajewsky,   Max-Delbruck-Ctr. for Molecular Medicine
Strain of Origin		129P2/OlaHsd
Promoter		Igh, immunoglobulin heavy chain complex, mouse, laboratory
General Note		The targeted IgH allele was of the a allotype.
Molecular Note		Homologous recombination and subsequent in vitro cre mediated excision resulted in the replacement of endogenous sequence encompassing a 3' Igh-D element (DQ52) and the Igh-J elements with a recombined antibody variable region derived from a 4-hydroxy-3-nitrophenyl acetyl binding antibody (B1-8). The B1-8 variable region was modified to contain a point mutation in codon 92, inactivating the heptameric recombination signal sequence. Flow cytometry verified cell surface expression of the mutant protein product. [MGI Ref ID J:79556]

Genotyping

Genotyping Information

Genotyping Protocols

Igh^tm2Cgn, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Sonoda E; Pewzner-Jung Y; Schwers S; Taki S; Jung S; Eilat D; Rajewsky K. 1997. B cell development under the condition of allelic inclusion. Immunity 6(3):225-33. [PubMed: 9075923]  [MGI Ref ID J:79556]

Additional References

Igh^tm2Cgn related

Baba M; Keller JR; Sun HW; Resch W; Kuchen S; Suh HC; Hasumi H; Hasumi Y; Kieffer-Kwon KR; Gonzalez CG; Hughes RM; Klein ME; Oh HF; Bible P; Southon E; Tessarollo L; Schmidt LS; Linehan WM; Casellas R. 2012. The folliculin-FNIP1 pathway deleted in human Birt-Hogg-Dube syndrome is required for murine B-cell development. Blood 120(6):1254-61. [PubMed: 22709692]  [MGI Ref ID J:189078]

Boboila C; Yan C; Wesemann DR; Jankovic M; Wang JH; Manis J; Nussenzweig A; Nussenzweig M; Alt FW. 2010. Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4. J Exp Med 207(2):417-27. [PubMed: 20142431]  [MGI Ref ID J:158825]

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]

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]

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]

Gauld SB; Benschop RJ; Merrell KT; Cambier JC. 2005. Maintenance of B cell anergy requires constant antigen receptor occupancy and signaling. Nat Immunol 6(11):1160-7. [PubMed: 16200069]  [MGI Ref ID J:112605]

Gonzalez SF; Lukacs-Kornek V; Kuligowski MP; Pitcher LA; Degn SE; Kim YA; Cloninger MJ; Martinez-Pomares L; Gordon S; Turley SJ; Carroll MC. 2010. Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes. Nat Immunol 11(5):427-34. [PubMed: 20305659]  [MGI Ref ID J:158970]

Good-Jacobson KL; Szumilas CG; Chen L; Sharpe AH; Tomayko MM; Shlomchik MJ. 2010. PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol 11(6):535-42. [PubMed: 20453843]  [MGI Ref ID J:160698]

Gu Y; Seidl KJ; Rathbun GA; Zhu C; Manis JP; van der Stoep N; Davidson L; Cheng HL; Sekiguchi JM; Frank K; Stanhope-Baker P; Schlissel MS; Roth DB; Alt FW. 1997. Growth retardation and leaky SCID phenotype of Ku70-deficient mice. Immunity 7(5):653-65. [PubMed: 9390689]  [MGI Ref ID J:44361]

Guo C; Yoon HS; Franklin A; Jain S; Ebert A; Cheng HL; Hansen E; Despo O; Bossen C; Vettermann C; Bates JG; Richards N; Myers D; Patel H; Gallagher M; Schlissel MS; Murre C; Busslinger M; Giallourakis CC; Alt FW. 2011. CTCF-binding elements mediate control of V(D)J recombination. Nature 477(7365):424-30. [PubMed: 21909113]  [MGI Ref ID J:176649]

Heizmann B; Reth M; Infantino S. 2010. Syk is a dual-specificity kinase that self-regulates the signal output from the B-cell antigen receptor. Proc Natl Acad Sci U S A 107(43):18563-8. [PubMed: 20940318]  [MGI Ref ID J:165501]

Ji Y; Resch W; Corbett E; Yamane A; Casellas R; Schatz DG. 2010. The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell 141(3):419-31. [PubMed: 20398922]  [MGI Ref ID J:160370]

Lansford R; Manis JP; Sonoda E; Rajewsky K; Alt FW. 1998. Ig heavy chain class switching in Rag-deficient mice. Int Immunol 10(3):325-32. [PubMed: 9576620]  [MGI Ref ID J:47240]

Le TV; Kim TH; Chaplin DD. 2008. Intraclonal competition inhibits the formation of high-affinity antibody-secreting cells. J Immunol 181(9):6027-37. [PubMed: 18941192]  [MGI Ref ID J:140743]

Li F; Eckhardt LA. 2009. A role for the IgH intronic enhancer E mu in enforcing allelic exclusion. J Exp Med 206(1):153-67. [PubMed: 19114667]  [MGI Ref ID J:144033]

Li F; Yan Y; Pieretti J; Feldman DA; Eckhardt LA. 2010. Comparison of Identical and Functional Igh Alleles Reveals a Nonessential Role for E{micro} in Somatic Hypermutation and Class-Switch Recombination. J Immunol 185(10):6049-57. [PubMed: 20937850]  [MGI Ref ID J:165636]

Liu H; Schmidt-Supprian M; Shi Y; Hobeika E; Barteneva N; Jumaa H; Pelanda R; Reth M; Skok J; Rajewsky K; Shi Y. 2007. Yin Yang 1 is a critical regulator of B-cell development. Genes Dev 21(10):1179-89. [PubMed: 17504937]  [MGI Ref ID J:121555]

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]

Manis JP; Dudley D; Kaylor L; Alt FW. 2002. IgH class switch recombination to IgG1 in DNA-PKcs-deficient B cells. Immunity 16(4):607-17. [PubMed: 11970883]  [MGI Ref ID J:113521]

Merrell KT; Benschop RJ; Gauld SB; Aviszus K; Decote-Ricardo D; Wysocki LJ; Cambier JC. 2006. Identification of anergic B cells within a wild-type repertoire. Immunity 25(6):953-62. [PubMed: 17174121]  [MGI Ref ID J:116779]

Minguet S; Dopfer EP; Schamel WW. 2010. Low-valency, but not monovalent, antigens trigger the B-cell antigen receptor (BCR). Int Immunol 22(3):205-12. [PubMed: 20145007]  [MGI Ref ID J:157926]

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]

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]

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]

Rubtsov A; Strauch P; Digiacomo A; Hu J; Pelanda R; Torres RM. 2005. Lsc regulates marginal-zone B cell migration and adhesion and is required for the IgM T-dependent antibody response. Immunity 23(5):527-38. [PubMed: 16286020]  [MGI Ref ID J:113295]

Spehalski E; Kovalchuk AL; Collins JT; Liang G; Dubois W; Morse HC 3rd; Ferguson DO; Casellas R; Dunnick WA. 2012. Oncogenic Myc translocations are independent of chromosomal location and orientation of the immunoglobulin heavy chain locus. Proc Natl Acad Sci U S A 109(34):13728-32. [PubMed: 22869734]  [MGI Ref ID J:188602]

Su IH; Basavaraj A; Krutchinsky AN; Hobert O; Ullrich A; Chait BT; Tarakhovsky A. 2003. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol 4(2):124-31. [PubMed: 12496962]  [MGI Ref ID J:83216]

Swanson CL; Wilson TJ; Strauch P; Colonna M; Pelanda R; Torres RM. 2010. Type I IFN enhances follicular B cell contribution to the T cell-independent antibody response. J Exp Med 207(7):1485-500. [PubMed: 20566717]  [MGI Ref ID J:163400]

Yan CT; Boboila C; Souza EK; Franco S; Hickernell TR; Murphy M; Gumaste S; Geyer M; Zarrin AA; Manis JP; Rajewsky K; Alt FW. 2007. IgH class switching and translocations use a robust non-classical end-joining pathway. Nature 449(7161):478-82. [PubMed: 17713479]  [MGI Ref ID J:126758]

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

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   17-AUG-11
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	100903 B6129PF2/J	(approximate)
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

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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Ordering Information
JAX^® Mice
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JAX^® Services
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Tel: 1-800-422-6423 or 1-207-288-5845
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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
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phone:	207-288-6470
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JAX^® Mice, Products & Services Conditions of Use

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