NOD.129S1(B6)-Tlr3^tm1Flv/LwnJ

Stock number: 029248
Product name: TLR3^-/-
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research

Description

TLR3^-/- mice may be useful in studies of the toll-like receptor pathway of innate immune response. On this NOD genetic background, mice are protected from Group B coxsackieviruses (CVB4)-induced (type 1 diabetes mellitus) T1DM.

Detailed description

The double-stranded 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 detects a truncated gene product (mRNA), which is not functional. TLR3^-/- NOD mice develop similar incidence of spontaneous type 1 diabetes to TLR3^+/- or TLR3^+/+ NOD mice. On this NOD congenic background, female TLR3^-/- mice are protected from Group B coxsackieviruses (CVB4)-induced (type 1 diabetes mellitus) T1DM.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these NOD/ShiLtJ-congenic mice could vary from that originally described on a B6;129 genetic background. We may modify the strain description if necessary as published results become available.

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 of the toll-like receptor 3 (Tlr3) gene. 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. Li Wen (Yale University) obtained these TLR3^-/- mice and backcrossed them to NOD/CaJ mice for 10 generations. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize NOD/ShiLtJ oocytes (from Stock No. 001976).

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.