In combination with immunoglobulin lambda light chain, this heavy chain variable (V) region produces antibody that binds hapten NP (4-hydroxy-3-nitrophenylacetyl). A Trp to Leu point mutation at codon 33 results in a 40-fold increase in antigen binding affinity (B1-8hi). 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.
Michel C Nussenzweig, The Rockefeller University
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted | Igh | immunoglobulin heavy chain complex |
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). A Trp to Leu point mutation at codon 33 results in a 40-fold increase in antigen binding affinity (B1-8hi). 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. The phenotype of this mutation on the BALB/cBy background is not known to differ from that on the C57BL/6 background (Stock No. 007594).
PCR was used to introduce a point mutation conferring higher affinity 4-hydroxy-3-nitrophenyl)acetyl (NP)-binding to Igh (VHB1-8): TGG->TTG (codon 33 Trp->Leu). A targeting vector incorporating a 5' floxed neomycin cassette in addition to the point mutation 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. Mice were backcrossed to C57BL/6 congenic background CD45.1 (Ptprca) mice for at least 12 generations by the donating laboratory, then backcrossed to BALB/cBy for 10 generations. This strain does not carry the Ptprca allele.
Allele Name | targeted mutation 1, Michel C Nussenzweig |
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Allele Type | Targeted |
Allele Synonym(s) | B1-8hi |
Gene Symbol and Name | Igh, immunoglobulin heavy chain complex |
Gene Synonym(s) | |
Promoter | Igh, immunoglobulin heavy chain complex, mouse, laboratory |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 12 |
Molecular Note | PCR was used to introduce a point mutation conferring higher affinity 4-hydroxy-3-nitrophenyl)acetyl (NP)-binding to Igh-V (VHB1-8): TGG->TTG (codon 33 Trp->Leu). A targeting vector incorporating a 5' floxed neomycin cassette in addition to the point mutation was transfected into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. |
Mutations Made By | Michel Nussenzweig, The Rockefeller University |
When maintained as a live colony, homozygous animals may be bred.
When using the CBy.129P2(B6)-Ightm1Mnz/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007775 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Igh<tm1Mnz> |
Frozen Mouse Embryo | CBy.129P2(B6)-Igh<tm1Mnz>/J | $2595.00 |
Frozen Mouse Embryo | CBy.129P2(B6)-Igh<tm1Mnz>/J | $2595.00 |
Frozen Mouse Embryo | CBy.129P2(B6)-Igh<tm1Mnz>/J | $3373.50 |
Frozen Mouse Embryo | CBy.129P2(B6)-Igh<tm1Mnz>/J | $3373.50 |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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