This double targeted mutation of the immunoglobulin kappa chain complex (Igk) and immunoglobulin heavy chain complex (Igh) genes displays an almost monoclonal B cell population and may be useful in studies of B cell development, receptor editing, tolerance and antibody diversification.
Klaus Rajewsky, Max-Delbruck-Ctr. for Molecular Medicine
|Allele Type||Gene Symbol||Gene Name|
|Targeted||Igh||immunoglobulin heavy chain complex|
|Allele Type||Gene Symbol||Gene Name|
|Targeted||Igk||immunoglobulin kappa chain complex|
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. As expected, most splenic B cells express the 3-83 idiotype, but total B cell number may be lower than wild-type. The 3-83 antibody is non-autoreactive on the H-2d background, while it is autoreactive on the H-2b and H-2k backgrounds. Mice heterozygous for both mutations and/or the H-2b and H-2k backgrounds exhibit an increase in frequency and absolute number of lambda-expressing B lymphocytes and a decrease in the expression of the 3-83 idiotype due to Igk RS recombination and Vl to Jl rearrangements. The 3-83KiJk<-> allele lacks endogenous Jk segments, preventing secondary Vk to Jk rearrangements. Mice homozygous for both mutations on the H-2d, but not H-2b and H-2k backgrounds, do not retain 3-83 expression and do not have Vk to Jk recombination events.This strain generates an almost monoclonal B cell population. This mutant mouse strain may be useful in studies of B cell development, receptor editing, tolerance and antibody diversification.
The targeting at the Igh locus was performed to replace the DNA region from upstream of DQ52 to downstream of JH4 with a vector that contains a loxP-flanked neo cassette, followed by the Ig 3-83 heavy chain gene, which includes its promoter region and the rearranged VDJ (with JH1). The construct was electroporated into 129P2/OlaHsd-derived E14.1TG3B1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The neomycin cassette was removed by transient transfection with a Cre recombinase expressing plasmid leaving a single loxP site. The resulting chimeric animals were crossed to C57BL/6 mice.
The targeting at the Igk locus was performed to replace the DNA region from upstream of Jk1 to downstream of Jk5 with a vector that contains a loxP-flanked neo cassette, followed by the Ig 3-83 light (kappa-k) chain gene, which includes its promoter region and the rearranged VJ (with Jk2), removing all endogenous Jk segments and preventing secondary Vk-Jk rearrangements. The construct was electroporated into 129P2/OlaHsd-derived E14.1TG3B1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The neomycin cassette was removed by transient transfection with a Cre recombinase expressing plasmid leaving a single loxP site 5' to the Vk gene. The resulting chimeric animals were crossed to C57BL/6 mice. Mice carrying the two mutations were bred together and then backcrossed to BALB/c (H2d) for 10 generations.
|Allele Name||targeted mutation 2, Klaus Rajewsky|
|Allele Synonym(s)||3-83Hi; 3-83mCkappa; Ightm1Pld|
|Gene Symbol and Name||Igh, immunoglobulin heavy chain complex|
|Promoter||Igh, immunoglobulin heavy chain complex, mouse, laboratory|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||The rearranged 3-83 heavy chain was inserted into the IgHa locus via homologous recombination. A floxed neo selection cassette was also introduced and subsequently removed by Cre mediated recombination.|
|Allele Name||targeted mutation 2, Klaus Rajewsky|
|Allele Synonym(s)||3-83kappaiJkappa-; Igktm2Pld|
|Gene Symbol and Name||Igk, immunoglobulin kappa chain complex|
|Promoter||Igk, immunoglobulin kappa chain complex, mouse, laboratory|
|Strain of Origin||Not Specified|
|Molecular Note||A targeting vector was used to insert a recombined Vk3-83-Jk5 region where all endogenous Jkappa segments are deleted.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
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