C.129S1(B6)-Tlr3^tm1Flv/J

Stock number: 022459
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

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.

Detailed description

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.

Development

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⁺ Kitl^Sl-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

Symbol: Tlr3^tm1Flv
Name: targeted mutation 1, Richard A Flavell
MGI accession ID: MGI:2653138
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tlr3
Marker name: toll-like receptor 3
Chromosome: 8
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.