The recombination signal of Igkrs (immunoglobulin kappa chain recombining sequence; also called RS) was removed in these targeted mutation mice, blocking RS-mediated Igk inactivation. Receptor editing and self-tolerance are impaired in homozygotes, in some cases leading to autoantibody formation.
David Nemazee, The Scripps Research Institute
Igkrs (immunoglobulin kappa chain recombining sequence; also called RS) encodes sequences that rearrange to inactivate Igk (the immunoglobulin kappa chain complex) in developing B cells. It carries a canonical Ig gene recombination signal, and rearranges by V(D)J recombination to Vκ elements and to sites in the Jκ-Cκ intron. RS recombination results in deletion of the Cκ exon and silencing of the Igk complex.
The recombination signal of Igkrs was removed in these targeted mutation mice, blocking RS-mediated Igk inactivation. Receptor editing and self-tolerance are impaired in homozygotes, in some cases leading to autoantibody formation. Animals make fewer B cells expressing lambda chain, whereas λ versus κ isotype exclusion is only modestly affected. The mice do not show autoimmunity, though they have slightly elevated IgM anti-DNA antibodies. Homozygotes are fully viable and fertile.
The recombinational signal sequence of Igkrs was replaced by a loxP-flanked neomycin cassette through homologous recombination in 129Sv/Ev-derived embryonic stem cells. The neomycin cassette was excised from resultant mice through crosses with a Zp3-Cre strain. This strain was backcrossed at least ten times to C57BL/6J by the donating laboratory.
|Allele Name||targeted mutation 1, David Nemazee|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Igkrs, immunoglobulin kappa chain recombining segment|
|Strain of Origin||129|
|Molecular Note||The upstream recombination signal sequence (RSS) was replaced by a loxP flanked neomycin resistance gene. Founder mice were crossed with a transgenic mouse that expresses Cre in germline cells for the removal of the neomycin cassette. Genomic PCR and sequencing confirmed the 139 bp encompassing the RSS were replaced by 190 bp consisting of a loxP site flanked by vector sequence.|
Homozygotes and heterozygotes are viable and fertile.
When using the B6.129-Igkrstm1Nemz/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #023071 in your Materials and Methods section.