Macrophages derived from homozygous mice of this strain fail to produce inflammatory cytokines, IFN-alpha or IFN-beta when challenged with poly(I:C), polyinosine-polycytidylic acid, and splenocytes isolated from homozygotes do not respond to viral dsRNA and also have diminished IL-6 production. These mice are resistant to poly(I:C) induced shock and produce lower levels of IL-12. This mutant mouse strain may be useful in studies of the toll-like receptor pathway of innate immune response.
Dr. Richard A. Flavell, Yale University School of Medicine
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Northern blot analysis detects a truncated gene product (mRNA), which is not functional. Unlike wildtype macrophages, macrophages derived from these animals fail to produce inflammatory cytokines, IFN-alpha or IFN-beta when challenged with poly(I:C), polyinosine-polycytidylic acid, a synthetic dsRNA analog. Splenocytes isolated from homozygotes do not respond to viral dsRNA and have diminished IL-6 production. Mice homozygous for the mutation are resistant to poly(I:C) induced shock and produce lower levels of IL-12. This mutant mouse strain may be useful in studies of the toll-like receptor pathway of innate immune response.
A targeting vector containing a loxP site flanked neomycin resistance cassette and a herpes simplex virus thymidine kinase gene was used to disrupt exon 1. The construct was electroporated into 129S1/Sv-p+ Tyr+ KitlSl-J derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male mice were crossed to female C57BL/6 mice. Heterozygotes were intercrossed to generate homozygotes. These mutant mice were generated by Lena Alexopoulou in the laboratory of Richard Flavell (Yale University).
|Allele Name||targeted mutation 1, Richard A Flavell|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||TLR-; TLR3; Tlr3-|
|Gene Symbol and Name||Tlr3, toll-like receptor 3|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||The gene was disrupted by replacement of exon 1 with a floxed neo cassette via homologous recombination. Northern blot analysis detected a truncated transcript in mutant animals. The mutant transcript does not encode a functional protein.|
|Mutations Made By|| |
Lena Alexopoulou, Centre d'Immunologie de Marseille-Luminy
When maintaining a live colony, these mice can be bred as homozygotes. Expected coat color is agouti.
When using the TLR3 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #005217 in your Materials and Methods section.