B6.129-Tlr2^tm1Kir/J

Stock number: 004650
Product name: Tlr2 KO
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research

Description

Bone marrow derived macrophages of homozygous mice do not respond to spirochete (Borrelia burgdorferi) lipoprotein challenge, although non-lipoprotein sonicate stimulates activation. Arthritis due to B. burgdorferi infection, as assessed by rear ankle swelling, is more severe in mutant mice. Tissues of infected mutants can contain up to 100 times higher bacteria levels than those found in wildtype littermates. Elevated spirochete numbers persist 8 weeks post-infection. Homozygotes do not produce TNF-alpha or IL-6, and do not develop symptoms of illness when treated with leptospiral (Leptospira interrogans) lippolysaccharide (LPS). This mutant mouse strain may be useful in studies of host response to bacterial endotoxins such as septic shock.

Detailed description

Mice that are homozygous for the targeted mutation are viable, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of isolated peritoneal macrophages. Bone marrow derived macrophages do not respond to spirochete (Borrelia burgdorferi) lipoprotein challenge, although non-lipoprotein sonicate stimulates activation. Arthritis due to B. burgdorferi infection, as assessed by rear ankle swelling, is more severe in mutant mice. Tissues of infected mutants can contain up to 100 times higher bacteria levels than those found in wildtype littermates. Elevated spirochete numbers persist 8 weeks post-infection. Homozygotes do not produce TNF-alpha or IL-6, and do not develop symptoms of illness when treated with leptospiral (Leptospira interrogans) lippolysaccharide (LPS). This mutant mouse strain may be useful in studies of host response to bacterial endotoxins such as septic shock.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt sequence of the targeted gene encoding the C-terminus of the extracellular and part of the transmembrane domains. The construct was electroporated into 129/SvJ derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Heterozygotes were intercrossed, and then backcrossed to C57BL/6J for 9 generations before mice were sent to The Jackson Laboratory in 2003. Since that time, the strain has been backcrossed to C57BL/6J for at least 10 additional generations.

Allele

Symbol: Tlr2^tm1Kir
Name: targeted mutation 1, Carsten J Kirschning
MGI accession ID: MGI:2674036
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tlr2
Marker name: toll-like receptor 2
Chromosome: 3
Strain of origin: 129
Molecular note: Sequence encoding the extracellular domain and a portion of the transmembrane domain was replaced with a neo cassette inserted by homologous recombination. Protein was undetected by Western blot analysis of peritoneal macrophages obtained from homozygous mutant mice.