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   Donating Investigator Michel Nussenzweig,   The Rockefeller University

Description
Mice homozygous for this targeted mutation are viable and fertile and do not display any gross physical or behavioral abnormalities. In combination with immunoglobulin lambda light chain, this heavy chain variable (V) region produces antibody that binds hapten NP (4-hydroxy-3-nitrophenylacetyl). An Ala to Gly point mutation at codon 24, Ser to Thr point mutation at codon 31, and a His to Gln point mutation at codon 35 result in low binding affinity for antigen (B1-8^lo). Despite the significantly enhanced affinity for NP, there is only a 2-3 fold difference in the T-independent proliferative response of B cells that carry high or low affinity receptors. In T cell-dependent responses there is no difference in the ability of B1-8 high vs. B1-8 low affinity cells to enter germinal center reactions. However, high affinity B cells were recruited preferentially in response to both T cell-dependent and T cell-independent antigens. Expression has been verified by immunostaining cells that carry the mutation.

Development
PCR was used to introduce three point mutations conferring lower affinity 4-hydroxy-3-nitrophenyl)acetyl (NP)-binding to Igh (V_HB1-8): GCT->GGT (codon 24 Ala->Gly), AGC->ACC (codon 31 Ser->Thr), CAC-CAG (codon 35 His->Gln). A targeting vector incorporating a 5' floxed neomycin cassette in addition to the point mutations was transfected into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Positive clones were injected into C57BL/6 blastocysts, and the resulting chimeric males were bred to C57BL/6 EIIA-Cre females to delete the neomycin gene, and leave a loxP site. This strain has been backcrossed to C57BL/6 for more than 12 generations by the donating laboratory.

Related Strains

Strains carrying other alleles of Igh

012642	B6.129P2(C)-Ightm2Cgn/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

Igh^tm2Mnz/Igh^tm2Mnz

        B6.129P2-Igh^tm2Mnz

• cellular phenotype
• *normal* cellular phenotype
  • 3 and 5 days after immunization, there is no evidence of increased B cell apoptosis relative to wild-type   (MGI Ref ID J:75653)
• • increased B cell proliferation
    • mutant B cells in mice challenged with a T1-2 antigen (NP-Ficoll) undergo rapid proliferative expansion (from 3 to 14% of lymphocytes by 5 days after immunization   (MGI Ref ID J:75653)
    • in immunized mice, on day 2 there is a higher percentage of low-affinity B cells (20%) compared to wild-type cells (~3%)   (MGI Ref ID J:75653)
• immune system phenotype
• increased B cell proliferation
  • mutant B cells in mice challenged with a T1-2 antigen (NP-Ficoll) undergo rapid proliferative expansion (from 3 to 14% of lymphocytes by 5 days after immunization   (MGI Ref ID J:75653)
  • in immunized mice, on day 2 there is a higher percentage of low-affinity B cells (20%) compared to wild-type cells (~3%)   (MGI Ref ID J:75653)
• increased IgG level
  • 4-hydroxy-3-nitrophenyl)acetyl-specific (NP) IgM antibody production is greater than in wild-type   (MGI Ref ID J:75653)
• increased IgM level
  • NP-specific IgM antibody production is greater than in wild-type   (MGI Ref ID J:75653)
• hematopoietic system phenotype
• increased B cell proliferation
  • mutant B cells in mice challenged with a T1-2 antigen (NP-Ficoll) undergo rapid proliferative expansion (from 3 to 14% of lymphocytes by 5 days after immunization   (MGI Ref ID J:75653)
  • in immunized mice, on day 2 there is a higher percentage of low-affinity B cells (20%) compared to wild-type cells (~3%)   (MGI Ref ID J:75653)

View Research Applications

Research Applications

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

Immunology, Inflammation and Autoimmunity Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ightm2Mnz
Allele Name		targeted mutation 2, Michel C Nussenzweig
Allele Type		Targeted (knock-in)
Common Name(s)		B1-8lo;
Mutation Made By		Michel Nussenzweig,   The Rockefeller University
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/OlaHsd
Promoter		Igh, immunoglobulin heavy chain complex, mouse, laboratory
Molecular Note		The following point mutations were inserted into the VHB1-8 region: GCT to GGT (Ala24Gly), AGC to ACC (Ser31Thr), CAC to CAG (His35Gln), AGA to ACT (Arg98Thr). A floxed neo included in the vector was subsequently removed via cre mediated recombination. [MGI Ref ID J:75653]

Genotyping

Genotyping Information

Genotyping Protocols

Igh^tm1Mnz, High Resolution Melting
Igh^tm1Mnz, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Shih TA; Roederer M; Nussenzweig MC. 2002. Role of antigen receptor affinity in T cell-independent antibody responses in vivo. Nat Immunol 3(4):399-406. [PubMed: 11896394]  [MGI Ref ID J:75653]

Additional References

Igh^tm2Mnz related

Cadera EJ; Wan F; Amin RH; Nolla H; Lenardo MJ; Schlissel MS. 2009. NF-kappaB activity marks cells engaged in receptor editing. J Exp Med 206(8):1803-16. [PubMed: 19581408]  [MGI Ref ID J:151490]

Chappell CP; Draves KE; Giltiay NV; Clark EA. 2012. Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses. J Exp Med 209(10):1825-40. [PubMed: 22966002]  [MGI Ref ID J:191423]

Reina-San-Martin B; Difilippantonio S; Hanitsch L; Masilamani RF; Nussenzweig A; Nussenzweig MC. 2003. H2AX is required for recombination between immunoglobulin switch regions but not for intra-switch region recombination or somatic hypermutation. J Exp Med 197(12):1767-78. [PubMed: 12810694]  [MGI Ref ID J:120658]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

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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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