IRF4 KO Mouse

This mouse model with conditional deletion of IRF4 in germinal centre B cells lack post<U+0096>germinal centre plasma cells and are unable to differentiate memory B cells into plasma cells.

Contributors

Inventor Institute
Riccardo Dalla-Favera The Trustees of Columbia University in the City of New York
Cat. #: 154098
Research Fields: Cancer;Immunology
Target: IRF4
disease: B-Cell Differentiation
Model: Conditional KO
Zygosity: Homozygous
Strain: C57BL/6
Alternate name: Interferon Regulatory Factor 4, Multiple Myeloma Oncogene 1, NF-EM5, LSIRF, MUM1, SHEP8
Product description: The transcription factor IRF4 is required for the generation of plasma cells from antibody producing B cells. This mouse model with conditional deletion of IRF4 in germinal centre B cells lack postgerminal centre plasma cells and are unable to differentiate memory B cells into plasma cells. Plasma cell differentiation required IRF4 as well as the transcriptional repressor Blimp-1, which both acted 'upstream' of the transcription factor XBP-1. In addition, IRF4-deficient B cells have impaired expression of activation-induced deaminase and lacked class-switch recombination, suggesting an independent function for IRF4 in this process. Knockout of the IRF4 allele was induced in germinal center- derived B cells by crossing with C1-Cre mice.
Conditional: Yes
Conditional description: Conditional Knockout mouse of IRF4 upon recombination by Cre-recombinase
Genetic background: The vector to target IRF4 was a derivative of pEASY-FLOX containing a phosphoglycerate kinaseneomycin-resistance poly(A) cassette, the herpes simplex virus thymidine kinase gene, two loxP sites, as well as two frt sites, a promoterless gene encoding eGFP in the opposite orientation, a triple simian virus 40 poly(A) site in inverse orientation generated by PCR and joining of the fragments, a phosphoglycerate kinase promoter in the opposite orientation, and multiple unique restriction sites for cloning Irf4 segments corresponding to the homology arms. Successively inserted into the cloning sites of the vector were three DNA fragments of the 129/Sv Irf4 locus comprising the following: 2.3 kb of the region upstream of the Irf4 promoter region; the Irf4 promoter region up to 300 bp downstream of exon 2 containing the translational start site; and 4.7 kb of the region downstream of exon 2. The linearized vector was electroporated into W9.5 embryonic stem cells derived from 129/SvEvTac. Chimeras were obtained after injection of the targeted embryonic stem cell clones into blastocysts derived from C57BL/6 mice
Production details: The vector to target IRF4 was a derivative of pEASY-FLOX containing a phosphoglycerate kinase–neomycin-resistance poly(A) cassette, the herpes simplex virus thymidine kinase gene, two loxP sites, as well as two frt sites, a promoterless gene encoding eGFP in the opposite orientation, a triple simian virus 40 poly(A) site in inverse orientation generated by PCR and joining of the fragments, a phosphoglycerate kinase promoter in the opposite orientation, and multiple unique restriction sites for cloning Irf4 segments corresponding to the homology arms. Successively inserted into the cloning sites of the vector were three DNA fragments of the 129/Sv Irf4 locus comprising the following: 2.3 kb of the region upstream of the Irf4 promoter region; the Irf4 promoter region up to 300 bp downstream of exon 2 containing the translational start site; and 4.7 kb of the region downstream of exon 2. The linearized vector was electroporated into W9.5 embryonic stem cells derived from 129/SvEvTac. Chimeras were obtained after injection of the targeted embryonic stem cell clones into blastocysts derived from C57BL/6 mice
Shipping conditions: Embryo/Spermatoza- Dry Ice
References:

Klein et al. 2006. Nat Immunol. 7(7):773-82. PMID: 16767092.

Transcription factor IRF4 controls plasma cell differentiation and class-switch recombination.

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