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Genes & Alleles

Tlr3;   Tlr3tm1Flv;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Targeted Mutation Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Donating Investigator Richard Flavell,   Yale University School of Medicine Generation F?+N1F6 (27-APR-08)

Strain Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Northern blot analysis detects a truncated gene product (mRNA), which is not functional. Unlike wildtype macrophages, macrophages derived from these animals fail to produce inflammatory cytokines, IFN-alpha or IFN-beta when challenged with poly(I:C), polyinosine-polycytidylic acid, a synthetic dsRNA analog. Splenocytes isolated from homozygotes do not respond to viral dsRNA and have diminished IL-6 production. Mice homozygous for the mutation are resistant to poly(I:C) induced shock and produce lower levels of IL-12. This mutant mouse strain may be useful in studies of the toll-like receptor pathway of innate immune response.

Strain Development
A targeting vector 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. Heterozygotes were intercrossed to generate homozygotes. These mutant mice were generated by Lena Alexopoulou in the laboratory of Richard Flavell (Yale University).

Mammalian Phenotype Terms assigned by genotype Tlr3tm1Flv/Tlr3tm1Flv         involves: 129S1/Sv * C57BL/6 immune system phenotype *normal* immune system phenotype (MGI Ref ID J:72167) normal lymphocyte development normal expression of CD3, B220, CD4, and CD8 in thymocytes and splenocytes abnormal B cell physiology (MGI Ref ID J:72167) impaired expression of CD69, CD80, and CD86 in response to poly(I:C), but not LPS impaired expression of CD69 in response to viral genomic dsRNA from Type I Lang mammalian reovirus abnormal macrophage physiology (MGI Ref ID J:72167) impaired ability to produce IL6, IL12 and TNF-alpha in response to poly(I:C), a synthetic dsRNA analogue production of IL6, IL12, and TNF-alpha in response to LPS, PGN, LTA, zymosan, mannan, or CpG DNA was comparable to wild type controls decreased inflammatory response (MGI Ref ID J:72167) resistant to poly(I:C)-induced shock compared to wild type mice produced less IL12 after poly(I:C) i.p. injection The following phenotype information may relate to a genetic background differing from this JAX® Mice strain. Tlr3tm1Flv/Tlr3tm1Flv         involves: C57BL/6 immune system phenotype *normal* immune system phenotype (MGI Ref ID J:86617) upregulation of costimulatory molecules, CD40 and CD86, by peritoneal macrophages in response to dsRNA was preserved on this background abnormal macrophage physiology (MGI Ref ID J:86617) impaired ability to produce type I interferon and TNF-alpha in response to dsRNA, but not in response to LPS Tlr3tm1Flv/Tlr3tm1Flv         Background Not Specified immune system phenotype abnormal NK T cell physiology (MGI Ref ID J:88906) NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection, however this decrease is not as pronounced as in Tlr9CpG1 or Myd88tm1Aki homozygotes abnormal NK cell physiology (MGI Ref ID J:88906) NK and NK-T cell activation is significantly lower compared to C57BL/6 wild-type controls during mouse cytomegalovirus infection, however this decrease is not as pronounced as in Tlr9CpG1 or Myd88tm1Aki homozygotes abnormal cytokine secretion (MGI Ref ID J:88906) type 1 IFN, IFNgamma and IL-12 p40 levels are decreased compared to C57BL/6 wild-type controls following sublethal viral infection, however this decrease is not as pronounced as in Myd88tm1Aki homozygotes increased susceptibility to viral infection (MGI Ref ID J:88906) viral loads are significantly higher after mouse cytomegalovirus infection compared to C57BL/6 wild-type controls, however titers are not as high as in Tlr9CpG1 or Myd88tm1Aki homozygotes

Gene & Allele Details

Allele Symbol		Tlr3tm1Flv
Allele Name		targeted mutation 1, Richard A Flavell
Common Name(s)		TLR-; Tlr3-;
Mutation Made By		Lena Alexopoulou,   Centre d'Immunologie de Marseille-Luminy
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		W9.5/W95
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Tlr3, toll-like receptor 3
Chromosome		8
Gene Common Name(s)		AI957183; CD283; expressed sequence AI957183;
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. [MGI Ref ID J:72167]

Control Information

Allele	Control
Tlr3tm1Flv	101043 B6129SF1/J	(approximate)
Tlr3tm1Flv	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Genotyping Protocols

Tlr3^tm1Flv

Colony Maintenance

Breeding & Husbandry	This strain is maintained as a homozygote.
Diet Information	LabDiet® 5K52/5K67

Additional Web Information

JAX Notes, Summer 2005; 498. Toll-like Receptor JAX® Mice for Immunological Research.

Animal Health Reports

Room Number           AX12

Research Applications

This mouse can be used to support research in many areas including:

Tlr3^tm1Flv related

Cell Biology Research
Signal Transduction

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers (Tlr deficiency)
CD Antigens, Antigen Receptors, and Histocompatibility Markers (genes regulating susceptibility to infectious disease and endotoxin)
Immunodeficiency Associated with Other Defects

References

Selected Reference(s)

Alexopoulou L; Holt AC; Medzhitov R; Flavell RA. 2001. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413(6857):732-8. [PubMed: 11607032]  [MGI Ref ID J:72167]

Additional References

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Price and Supply Information

Strain Name:	B6;129S1-Tlr3tm1Flv/J
Stock Number:	005217

Price Details

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Supply Details

Standard Supply	Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes	Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.
Licensing	See General Terms and Conditions below for Licensing and Use Restrictions
Control Information	View Control Information in Strain Details.

General Terms and Conditions

View JAX^® Mice & Services Conditions of Use.

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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