Overview

Also Known As:B1-8 High Affinity (BALB/cByJ background)

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 (B1-8^hi). 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.

Donating Investigator

Michel C Nussenzweig, The Rockefeller University

Genetic overview

Genetic Background	Generation

Igh^tm1Mnz

Allele Type	Gene Symbol	Gene Name
Targeted	Igh	immunoglobulin heavy chain complex

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Research Applications

Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed 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). A Trp to Leu point mutation at codon 33 results in a 40-fold increase in antigen binding affinity (B1-8^hi). 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).

Development

PCR was used to introduce a point mutation conferring higher affinity 4-hydroxy-3-nitrophenyl)acetyl (NP)-binding to Igh (V_HB1-8): 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 (Ptprc^a) mice for at least 12 generations by the donating laboratory, then backcrossed to BALB/cBy for 10 generations. This strain does not carry the Ptprc^a allele.

Selected References

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

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Genetics

Igh^tm1Mnz

Allele Symbol: Igh^tm1Mnz

Allele Name	targeted mutation 1, Michel C Nussenzweig
Allele Type	Targeted
Allele Synonym(s)	B1-8^hi
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

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Igh^tm1Mnz/Igh^tm1Mnz
B6.129P2-Igh

cellular phenotype

abnormal cell cycle
- absolute number of cells in cell cycle is always higher than in Igh^tm2Mnz or wild-type mice

increased B cell apoptosis
- there are higher numbers of apoptotic mutant B cells than in wild-type or Igh^tm2Mnz B cells in spleens 3 and 5 days after immunization

increased B cell proliferation
- in immunized mice, on day 2 there is a much higher percentage of high-affinity B cells (58%) compared to wild-type cells (~3%)
- mutant B cells in mice challenged with a T1-2 antigen (NP-Ficoll) undergo rapid proliferative expansion (from 3 to 25% of lymphocytes by 5 days after immunization

immune system phenotype

abnormal B cell physiology
- cells whereas Igh^tm2Mnz B cells are not expanded
- after 5 days post immunization, 85% of plasmacytes and 60% of germinal center cells are Igh^tm1Mnz B cells (high affinity)
- fraction of mutant B cells differentiate into short lived germinal center (GC) cells; GC response is greater than in Igh^tm2Mnz cells
- mutant B cells with high affinity for antigen are preferentially selected during early phase of T1-2 immune response, over mutant B cells with low affinity for antigen
- some mutant B cells that express Ig lambda differentiate into short-lived plasmacytes in red pulp of lymphoid follicles; plasmacyte response is greater than in Igh^tm2Mnz cells or wild-type
- when equal numbers of Igh^tm1Mnz and Igh^tm2Mnz B cells are transferred to wild-type recipient mice, after immunization with NP-Ficoll, Igh^tm1Mnz B cells preferentially expand and proliferation to make up ~46% of Ig lambda B cells whereas Igh^tm2Mnz B cells are not expanded

increased B cell apoptosis
- there are higher numbers of apoptotic mutant B cells than in wild-type or Igh^tm2Mnz B cells in spleens 3 and 5 days after immunization

increased B cell proliferation
- in immunized mice, on day 2 there is a much higher percentage of high-affinity B cells (58%) compared to wild-type cells (~3%)
- mutant B cells in mice challenged with a T1-2 antigen (NP-Ficoll) undergo rapid proliferative expansion (from 3 to 25% of lymphocytes by 5 days after immunization

increased IgG level
- 4-hydroxy-3-nitrophenyl)acetyl-specific (NP) IgM antibody production is greater than in Igh^tm2Mnz B cells or wild-type

increased IgM level
- NP-specific IgM antibody production is greater than in Igh^tm2Mnz B cells or wild-type

hematopoietic system phenotype

abnormal B cell physiology
- cells whereas Igh^tm2Mnz B cells are not expanded
- after 5 days post immunization, 85% of plasmacytes and 60% of germinal center cells are Igh^tm1Mnz B cells (high affinity)
- fraction of mutant B cells differentiate into short lived germinal center (GC) cells; GC response is greater than in Igh^tm2Mnz cells
- mutant B cells with high affinity for antigen are preferentially selected during early phase of T1-2 immune response, over mutant B cells with low affinity for antigen
- some mutant B cells that express Ig lambda differentiate into short-lived plasmacytes in red pulp of lymphoid follicles; plasmacyte response is greater than in Igh^tm2Mnz cells or wild-type
- when equal numbers of Igh^tm1Mnz and Igh^tm2Mnz B cells are transferred to wild-type recipient mice, after immunization with NP-Ficoll, Igh^tm1Mnz B cells preferentially expand and proliferation to make up ~46% of Ig lambda B cells whereas Igh^tm2Mnz B cells are not expanded

increased B cell apoptosis
- there are higher numbers of apoptotic mutant B cells than in wild-type or Igh^tm2Mnz B cells in spleens 3 and 5 days after immunization

increased B cell proliferation
- in immunized mice, on day 2 there is a much higher percentage of high-affinity B cells (58%) compared to wild-type cells (~3%)
- mutant B cells in mice challenged with a T1-2 antigen (NP-Ficoll) undergo rapid proliferative expansion (from 3 to 25% of lymphocytes by 5 days after immunization

increased IgG level
- 4-hydroxy-3-nitrophenyl)acetyl-specific (NP) IgM antibody production is greater than in Igh^tm2Mnz B cells or wild-type

increased IgM level
- NP-specific IgM antibody production is greater than in Igh^tm2Mnz B cells or wild-type

References

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

Additional - Igh^tm1Mnz related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Igh
- Standard PCR:Ptprc Igh
- Standard PCR:Igh
- Genotyping resources and troubleshooting
Breeding Considerations

When maintained as a live colony, homozygous animals may be bred.
- Additional Breeding and Husbandry Support
Citation
When using the CBy.129P2(B6)-Igh^tm1Mnz/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007775 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Igh<tm1Mnz>

Related Products and Services

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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General Terms and Conditions

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Also Known As:B1-8 High Affinity (BALB/cByJ background)

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Ightm1Mnz

Allele Symbol: Ightm1Mnz

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ightm1Mnz/Ightm1MnzB6.129P2-Igh

cellular phenotype

immune system phenotype

hematopoietic system phenotype

References

Additional - Ightm1Mnz related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Igh^tm1Mnz

Allele Symbol: Igh^tm1Mnz

Genotype: Igh^tm1Mnz/Igh^tm1Mnz
B6.129P2-Igh

Additional - Igh^tm1Mnz related