Production of macrophage cytokines in response to stimulation with lipopolysaccharide, peptidoglycan and double-stranded RNA is reduced in these Ripk2 KO mice, making them suitable for use in studies of innate and adaptive immune system signaling.
Dr. Richard A. Flavell, Yale University School of MedicineRead More +
Rip2 KO mice contain a neo cassette in reverse orientation in place of exons 2-3 of the Ripk2 (receptor (TNFRSF)-interacting serine-threonine kinase 2) gene. Cytokine production in macrophages is reduced in homozygotes upon stimulation with lipopolysaccharide, peptidoglycan and double-stranded RNA, but not with bacterial DNA. RIPK2 deficient cells are also hyporesponsive to signaling through IL1 and IL18 interleukin receptors, and deficient for signaling through NOD (nucleotide-binding oligomerization domain) proteins. T cells show severely reduced NFKB (nuclear factor of kappa light chain gene enhancer in B-cells) activation, IL2 production and proliferation on T cell receptor (TCR) engagement, and impaired differentiation to T-helper subtype 1 (TH1)cells. Western blot analysis of thymocytes demonstrates the absence of protein in homozygous mutant mice. Homozygotes are viable and fertile.
A targeting vector was designed to replace exons 2-3 of the receptor (TNFRSF)-interacting serine-threonine kinase 2 (Ripk2) gene, encoding the active site aspartate residue, with a loxP-flanked neomycin resistance cassette in the opposite orientation to the gene. The vector was linearized and injected into 129S1/Sv-derived W9.5 embryonic stem (ES) cells. Targeted clones were injected into C57BL/6 blastocysts. Resultant chimeric mice were backcrossed to C57BL/6 for 10 generations by the donating laboratory (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. One of the 27 markers on Chromosome 4 is segregating, likly due to targeted mutation. All 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Allele Name||targeted mutation 1, Richard A Flavell|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||RICK-; Rip2-|
|Gene Symbol and Name||Ripk2, receptor (TNFRSF)-interacting serine-threonine kinase 2|
|Gene Synonym(s)||2210420D18Rik; 2210420D18Rik; CARD3; CARDIAK; CCK; D4Bwg0615e; D4Bwg0615e; DNA segment, Chr 4, Brigham & Women's Genetics 0615 expressed; GIG30; RICK; RIKEN cDNA 2210420D18 gene; RIP2|
|Strain of Origin||129S1/Sv-Oca2<+> Tyr<+> Kitl<+>|
|Molecular Note||The gene was disrupted by replacement of exons 2 and 3 with a neomycin resistance gene by homologous recombination. Absence of gene expression in homozygous mutant animals was confirmed by Western blot analysis of thymocyte extracts.|
|Mutations Made By|| |
Dr. Richard Flavell, Yale University School of Medicine
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