Podocytes derived from homozygous mice of this strain fail to respond to viral dsRNA. This mutant mouse strain may be useful in studies of the toll-like receptor pathway of innate immune response.
Steven N. Emancipator, Case Western Reserve University
The doublestranded RNA pathogen-associated molecular patterns (PAMPs) associated with viral infections (specifically replicating viruses) and with necrotic cells, are recognized by toll-like receptor 3 (TLR3), which then induces the activation of NF-kappaB and the production of type I interferons. These mice carry a targeted mutation of the Tlr3, toll-like receptor 3, gene, in which exon 1 is disrupted. Mice that are homozygous for the targeted mutation are viable and fertile. Northern blot analysis of homozygotes on the B6;129S1 background detects a truncated gene product (mRNA), which is not functional. Podocytes derived from homozygotes on the congenic BALB/cJ background do not respond to extracellular dsRNA and transfected dsRNA suppresses wound healing in an in vitro assay. During backcrossing, the Y chromosome may not have been fixed to the BALB/cJ genetic background.
A targeting vector designed by Drs. Lena Alexopoulou in the laboratory of Richard Flavell (Yale University) 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. Dr. Steven N. Emancipator (Case Western Reserve University) obtained these Stock No. 005217 and backcrossed the mice to BALB/cJ (Stock No. 000651) for 12 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to BALB/cJ (Stock No. 000651) at least once to establish the colony.
|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.
When using the C.129S1(B6)-Tlr3tm1Flv/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022459 in your Materials and Methods section.