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
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.
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.
|Allele Name||targeted mutation 1, Michel C Nussenzweig|
|Gene Symbol and Name||Igh, immunoglobulin heavy chain complex|
|Promoter||Igh, immunoglobulin heavy chain complex, mouse, laboratory|
|Strain of Origin||129P2/OlaHsd|
|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
|Allele Name||a variant|
|Allele Type||Not Applicable|
|Allele Synonym(s)||CD45.1; Ly5a; PtprcSJL|
|Gene Symbol and Name||Ptprc, protein tyrosine phosphatase, receptor type, C|
|Site of Expression||Widely expressed on all adaptive and innate immune cells.|
|Strain of Origin||Not Applicable|
|Molecular Note||Ptprca is found in strains SJL/J, STS/A, and DA. Ptprcb is found in strains C57BL/6, C3H/An, DBA/2, AKR, and many others (J:13367, J:12054, J:12077, J:8603). Twelve nucleotide differences between the a and b alleles have been identified. These base substitutions correspond to five amino-acid changes within the extracellular domain of the encoded protein. These amino-acid differences are clustered in a region that also contains the greatest divergence between mouse and rat sequences (J:22485). |
Note that the allele designations originally described were reversed in 1987 (J:8603); all publications prior to 1987 show SJL/J, STS/A, and DA as having the b allele and the C57BL/6J group as having the a allele (J:22341).
When maintained as a live colony, heterozygotes or homozygotes may be bred.
When using the B6.129P2-Ptrpca Ightm1Mnz/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007594 in your Materials and Methods section.
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