Strain Name:

B6.129P2-Ptrpca Ightm1Mnz/J

Stock Number:

007594

Availability:

Repository-Cryopreserved

Use Restrictions Apply, see Terms of Use
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.

Description

Strain Information

Former Names B6.129P2-Ptprca Igh-Vtm1Mnz/J    (Changed: 11-JUL-07 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory 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). 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.

Development
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.

Related Strains

Strains carrying   Ightm1Mnz allele
007775   CBy.129P2(B6)-Ightm1Mnz/J
View Strains carrying   Ightm1Mnz     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Ightm1Mnz/Ightm1Mnz

        B6.129P2-Ightm1Mnz
  • immune system phenotype
  • abnormal B cell physiology (MGI Ref ID J:75653)
    • 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 Ightm2Mnz cells or wild-type
    • fraction of mutant B cells differentiate into short lived germinal center (GC) cells; GC response is greater than in Ightm2Mnz cells
    • when equal numbers of Ightm1Mnz and Ightm2Mnz B cells are transferred to wild-type recipient mice, after immunization with NP-Ficoll, Ightm1Mnz B cells preferentially expand and proliferation to make up ~46% of Ig lambda B cells whereas Ightm2Mnz B cells are not expanded
    • after 5 days post immunization, 85% of plasmacytes and 60% of germinal center cells are Ightm1Mnz B cells (high affinity)
    • 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
    • increased B cell proliferation (MGI Ref ID J:75653)
      • 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
      • in immunized mice, on day 2 there is a much higher percentage of high-affinity B cells (58%) compared to wild-type cells (~3%)
    • increased IgG level (MGI Ref ID J:75653)
      • 4-hydroxy-3-nitrophenyl)acetyl-specific (NP) IgM antibody production is greater than in Ightm2Mnz B cells or wild-type
    • increased IgM level (MGI Ref ID J:75653)
      • NP-specific IgM antibody production is greater than in Ightm2Mnz B cells or wild-type
  • increased B cell apoptosis (MGI Ref ID J:75653)
    • there are higher numbers of apoptotic mutant B cells than in wild-type or Ightm2Mnz B cells in spleens 3 and 5 days after immunization
  • cellular phenotype
  • abnormal cell cycle (MGI Ref ID J:75653)
    • absolute number of cells in cell cycle is always higher than in Ightm2Mnz or wild-type mice
  • hematopoietic system phenotype
  • increased B cell apoptosis (MGI Ref ID J:75653)
    • there are higher numbers of apoptotic mutant B cells than in wild-type or Ightm2Mnz B cells in spleens 3 and 5 days after immunization
  • increased B cell proliferation (MGI Ref ID J:75653)
    • 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
    • in immunized mice, on day 2 there is a much higher percentage of high-affinity B cells (58%) compared to wild-type cells (~3%)
View Research Applications

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

Immunology and Inflammation Research

Igh related

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

Genes & Alleles

Gene & Allele Information

Allele Symbol Ightm1Mnz
Allele Name targeted mutation 1, Michel C Nussenzweig
Allele Type Targeted (knock-in)
Common Name(s) B1-8hi;
Mutation Made By Michel Nussenzweig,   The Rockefeller University
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14
ES Cell Line Strain129P2/OlaHsd
Gene Symbol and Name Igh, immunoglobulin heavy chain complex
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. [MGI Ref ID J:75653]
Gene Symbol and Name Ptprc, protein tyrosine phosphatase, receptor type, C
Chromosome 1
Gene Common Name(s) B220; CD45; CD45 antigen; CD45R; Cd45; GP180; L-CA; LCA; LY5; Ly-5; Lyt-4; RT7; T-lymphocyte antigen 4; T200; lymphocyte antigen 5;

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

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

Ightm1Mnz related

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

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
*Price(s) in US dollars ($)

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
*Price(s) in US dollars ($)

Additional Supply Details

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.

General Terms and Conditions


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Terms of Use


General Terms and Conditions


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