B6(Cg)-Tlr5^tm1.2Gewr/J

Stock number: 028909
Product name: TLR5 null (TLR5^-)
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

The TLR5 null allele (TLR5^-) mice have exon 4 of the toll-like receptor 5 gene deleted. These knock-out mice may be useful in studying TLR5 recognition of pathogens, cytokine secretion and activation of innate immune responses.
Of note, a C57BL/6-congenic TLR5 floxed exon 4 allele (TLR5^fl) is also available as Stock No. 028599.

Detailed description

The Tlr5 gene encodes toll-like receptor 5, which has a fundamental role in bacteria recognition and activation of innate immune responses. TLR5 is the receptor for bacterial flagellin, acting via MYD88 and TRAF6; leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.
The TLR5 null allele (TLR5^-) has exon 4 of the toll-like receptor 5 gene deleted throughout the germline. No functional protein is expressed from this knockout allele. Homozygous mice (TLR5^-/-) are expected to exhibit increased levels of flagellated bacteria in the intestine, that will promote low-grade inflammation, metabolic syndrome and colitis.

In response to scientific interest, we may offer floxed alleles as well as their resulting germline-knockout alleles. The knockout phenotype described above was for C57BL/6-congenic TLR5^fl mice (Stock No. 028599) bred to C57BL/6-congenic mice expressing non-germline Cre recombinase. It should be noted that the phenotype of these C57BL/6-congenic TLR5 null mice (Stock No. 028909) could vary from that expected/inferred from other similar models. We may modify this strain description if necessary as published results become available.

Development

The TLR5 null allele (TLR5^-) was generated by breeding TLR5^fl mice with the germline cre-expressing Sox2-Cre mouse line, and then removing the Sox2-Cre allele. Specific details below.
The TLR5^fl strain was created by Dr. Andrew T. Gewirtz and Benoit Chassaing (Georgia State University) to have loxP sites flanking exon 4 of toll-like receptor 5 gene (Tlr5) on chromosome 1. TLR5^fl mice on a C57BL/6-congenic background arrived at The Jackson Laboratory Repository in 2016 as Stock No. 028599. Upon arrival, some floxed animals were bred at least one additional generation to C57BL/6NJ inbred mice (Stock No. 005304). Next, they were bred to the germline cre-expressing, C57BL/6-congenic Sox2-Cre strain (Stock No. 008454). The resulting animals with the TLR5 null allele (TLR5^-) were bred together or to wildtype (and the Sox2-Cre transgene was removed). The C57BL/6-congenic TLR5^- colony is Stock No. 028909. The genetic background is expected to be a mix of C57BL/6J and C57BL/6N.

Allele

Symbol: Tlr5^tm1.2Gewr
Name: targeted mutation 1.2, Andrew Gewirtz
MGI accession ID: MGI:5780549
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tlr5
Marker name: toll-like receptor 5
Chromosome: 1
Strain of origin: C57BL/6NTac
Molecular note: A targeting vector was designed to place a loxP site upstream of exon 4, and a FRT::loxP::Neo::FRT::loxP cassette inserted 211 base pairs downstream of exon 4. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 4 floxed. Cre-mediated recombination removed exon 4.