Description

Strain Information

Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Hemizygote         (Female x Male)   06-DEC-11 Species laboratory mouse Generation N10+F9 (05-FEB-09) Generation Definitions   Donating Investigator Dr. Richard A. Flavell,   Yale University School of Medicine

Description
These toll-like receptor 7 targeted mutation mice may be useful in studies of viral immunity. Homozygotes demonstrate reduced responses to in vivo infection with vesicular stomatitis virus. This emphasizes the roll of the gene in viral recognition by plasmacytoid dendritic cells and B cells which activate costimulatory molecules and produce cytokines. No RNA expression is detected in bone marrow-derived macrophages by Northern blot analysis. The lacZ reporter introduced under the gene's promoter shows that within mesenteric lymph nodes, expression is normally confined to the perifollicular regions. Homozygotes are viable, fertile, have no obvious developmental problems, but are poor breeders for unknown reasons.

Development
A segment of exon 3 was replaced by a lacZ gene and loxP-flanked neomycin resistance cassette. The targeting vector was introduced to 129S1/Sv-p⁺ Tyr⁺ Kitl⁺-derived CJ7 embryonic stem (ES) cells. This line was backcrossed ten times to C57BL/6Ncr by the donating laboratory. Upon arrival at The Jackson Laboratory, this strain was crossed one time to C57BL/6J.

Control Information

	Control
	005304 C57BL/6NJ	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tlr7^tm1Flv/Tlr7^tm1Flv

        B6.129S1-Tlr7^tm1Flv

• immune system phenotype
• decreased IgG level
  • in the serum and as glomerular deposition   (MGI Ref ID J:165267)
• • decreased IgG1 level   (MGI Ref ID J:165267)
  • decreased IgG2a level   (MGI Ref ID J:165267)
• decreased IgM level
  • in the serum and as glomerular deposition   (MGI Ref ID J:165267)
• decreased anti-insulin autoantibody level   (MGI Ref ID J:165267)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Tlr7^tm1Flv/Tlr7^tm1Flv

        involves: 129S1/Sv

• immune system phenotype
• decreased circulating interferon-alpha level
  • while IFNalpha secretion in response to infection with vesicular stomatitis virus (a ssRNA virus) was similar to controls, serum levels of IFNalpha were reduced after infection relative to controls   (MGI Ref ID J:89257)
• homeostasis/metabolism phenotype
• decreased circulating interferon-alpha level
  • while IFNalpha secretion in response to infection with vesicular stomatitis virus (a ssRNA virus) was similar to controls, serum levels of IFNalpha were reduced after infection relative to controls   (MGI Ref ID J:89257)

View Research Applications

Research Applications

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

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
      Tlr deficiency
      genes regulating susceptibility to infectious disease and endotoxin
Immunodeficiency
      Tlr deficiency
Inflammation
      Tlr deficiency

Virology Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tlr7tm1Flv
Allele Name		targeted mutation 1, Richard A Flavell
Allele Type		Targeted (Reporter)
Common Name(s)		Tlr7-;
Mutation Made By		Dr. Richard Flavell,   Yale University School of Medicine
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		CJ7
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Tlr7, toll-like receptor 7
Chromosome		X
Gene Common Name(s)		RGD1563357; TLR7-like;
Molecular Note		A cassette containing lacZ and floxed neo replaced a portion of exon 3. Northern blot analysis of mutant bone marrow-derived macrophages indicated no mRNA was present. Beta galactose staining showed expression of lacZ in mutant lymph nodes. [MGI Ref ID J:102090] [MGI Ref ID J:89257]

Genotyping

Genotyping Information

Genotyping Protocols

Tlr7^tm1Flv, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lund JM; Alexopoulou L; Sato A; Karow M; Adams NC; Gale NW; Iwasaki A; Flavell RA. 2004. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci U S A 101(15):5598-603. [PubMed: 15034168]  [MGI Ref ID J:89257]

Additional References

Tlr7^tm1Flv related

Browne EP. 2011. Toll-like receptor 7 controls the anti-retroviral germinal center response. PLoS Pathog 7(10):e1002293. [PubMed: 21998589]  [MGI Ref ID J:183184]

Buechler MB; Teal TH; Elkon KB; Hamerman JA. 2013. Cutting edge: Type I IFN drives emergency myelopoiesis and peripheral myeloid expansion during chronic TLR7 signaling. J Immunol 190(3):886-91. [PubMed: 23303674]  [MGI Ref ID J:193249]

Chen A; Ahlen G; Brenndorfer ED; Brass A; Holmstrom F; Chen M; Soderholm J; Milich DR; Frelin L; Sallberg M. 2011. Heterologous T cells can help restore function in dysfunctional hepatitis C virus nonstructural 3/4A-specific T cells during therapeutic vaccination. J Immunol 186(9):5107-18. [PubMed: 21430225]  [MGI Ref ID J:172864]

Christensen SR; Shupe J; Nickerson K; Kashgarian M; Flavell RA; Shlomchik MJ. 2006. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity 25(3):417-28. [PubMed: 16973389]  [MGI Ref ID J:113557]

Deane JA; Pisitkun P; Barrett RS; Feigenbaum L; Town T; Ward JM; Flavell RA; Bolland S. 2007. Control of Toll-like Receptor 7 Expression Is Essential to Restrict Autoimmunity and Dendritic Cell Proliferation. Immunity 27(5):801-10. [PubMed: 17997333]  [MGI Ref ID J:127600]

Demaria O; Pagni PP; Traub S; de Gassart A; Branzk N; Murphy AJ; Valenzuela DM; Yancopoulos GD; Flavell RA; Alexopoulou L. 2010. TLR8 deficiency leads to autoimmunity in mice. J Clin Invest 120(10):3651-62. [PubMed: 20811154]  [MGI Ref ID J:165267]

Fabbri M; Paone A; Calore F; Galli R; Gaudio E; Santhanam R; Lovat F; Fadda P; Mao C; Nuovo GJ; Zanesi N; Crawford M; Ozer GH; Wernicke D; Alder H; Caligiuri MA; Nana-Sinkam P; Perrotti D; Croce CM. 2012. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci U S A 109(31):E2110-6. [PubMed: 22753494]  [MGI Ref ID J:188409]

Gregorio J; Meller S; Conrad C; Di Nardo A; Homey B; Lauerma A; Arai N; Gallo RL; Digiovanni J; Gilliet M. 2010. Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. J Exp Med 207(13):2921-30. [PubMed: 21115688]  [MGI Ref ID J:176867]

Herlands RA; Christensen SR; Sweet RA; Hershberg U; Shlomchik MJ. 2008. T Cell-Independent and Toll-like Receptor-Dependent Antigen-Driven Activation of Autoreactive B Cells. Immunity 29(2):249-60. [PubMed: 18691914]  [MGI Ref ID J:139567]

Ichinohe T; Pang IK; Iwasaki A. 2010. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat Immunol 11(5):404-10. [PubMed: 20383149]  [MGI Ref ID J:158948]

Jeisy-Scott V; Davis WG; Patel JR; Bowzard JB; Shieh WJ; Zaki SR; Katz JM; Sambhara S. 2011. Increased MDSC accumulation and Th2 biased response to influenza A virus infection in the absence of TLR7 in mice. PLoS One 6(9):e25242. [PubMed: 21966467]  [MGI Ref ID J:177864]

Jeisy-Scott V; Kim JH; Davis WG; Cao W; Katz JM; Sambhara S. 2012. TLR7 Recognition Is Dispensable for Influenza Virus A Infection but Important for the Induction of Hemagglutinin-Specific Antibodies in Response to the 2009 Pandemic Split Vaccine in Mice. J Virol 86(20):10988-98. [PubMed: 22837197]  [MGI Ref ID J:187889]

Kolli D; Bao X; Liu T; Hong C; Wang T; Garofalo RP; Casola A. 2011. Human metapneumovirus glycoprotein G inhibits TLR4-dependent signaling in monocyte-derived dendritic cells. J Immunol 187(1):47-54. [PubMed: 21632720]  [MGI Ref ID J:176038]

Lamere MW; Lam HT; Moquin A; Haynes L; Lund FE; Randall TD; Kaminski DA. 2011. Contributions of Antinucleoprotein IgG to Heterosubtypic Immunity against Influenza Virus. J Immunol 186(7):4331-9. [PubMed: 21357542]  [MGI Ref ID J:170689]

Liu T; Berta T; Xu ZZ; Park CK; Zhang L; Lu N; Liu Q; Liu Y; Gao YJ; Liu YC; Ma Q; Dong X; Ji RR. 2012. TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice. J Clin Invest 122(6):2195-207. [PubMed: 22565312]  [MGI Ref ID J:188291]

Liu T; Xu ZZ; Park CK; Berta T; Ji RR. 2010. Toll-like receptor 7 mediates pruritus. Nat Neurosci 13(12):1460-2. [PubMed: 21037581]  [MGI Ref ID J:166905]

Neighbours LM; Long K; Whitmore AC; Heise MT. 2012. Myd88-dependent toll-like receptor 7 signaling mediates protection from severe ross river virus-induced disease in mice. J Virol 86(19):10675-85. [PubMed: 22837203]  [MGI Ref ID J:187888]

Nickerson KM; Christensen SR; Shupe J; Kashgarian M; Kim D; Elkon K; Shlomchik MJ. 2010. TLR9 regulates TLR7- and MyD88-dependent autoantibody production and disease in a murine model of lupus. J Immunol 184(4):1840-8. [PubMed: 20089701]  [MGI Ref ID J:159472]

Ochi A; Graffeo CS; Zambirinis CP; Rehman A; Hackman M; Fallon N; Barilla RM; Henning JR; Jamal M; Rao R; Greco S; Deutsch M; Medina-Zea MV; Bin Saeed U; Ego-Osuala MO; Hajdu C; Miller G. 2012. Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans. J Clin Invest 122(11):4118-29. [PubMed: 23023703]  [MGI Ref ID J:192739]

Oh JZ; Kurche JS; Burchill MA; Kedl RM. 2011. TLR7 enables cross-presentation by multiple dendritic cell subsets through a type I IFN-dependent pathway. Blood 118(11):3028-38. [PubMed: 21813451]  [MGI Ref ID J:177064]

Pang IK; Ichinohe T; Iwasaki A. 2013. IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8(+) T cell responses to influenza A virus. Nat Immunol 14(3):246-53. [PubMed: 23314004]  [MGI Ref ID J:193240]

Parker D; Prince A. 2012. Staphylococcus aureus induces type I IFN signaling in dendritic cells via TLR9. J Immunol 189(8):4040-6. [PubMed: 22962685]  [MGI Ref ID J:190532]

Seo YJ; Pritzl CJ; Vijayan M; Blake CR; McClain ME; Hahm B. 2012. Sphingosine analogue AAL-R increases TLR7-mediated dendritic cell responses via p38 and type I IFN signaling pathways. J Immunol 188(10):4759-68. [PubMed: 22490865]  [MGI Ref ID J:188687]

Town T; Bai F; Wang T; Kaplan AT; Qian F; Montgomery RR; Anderson JF; Flavell RA; Fikrig E. 2009. Toll-like receptor 7 mitigates lethal West Nile encephalitis via interleukin 23-dependent immune cell infiltration and homing. Immunity 30(2):242-53. [PubMed: 19200759]  [MGI Ref ID J:146461]

Traub S; Demaria O; Chasson L; Serra F; Desnues B; Alexopoulou L. 2012. Sex bias in susceptibility to MCMV infection: implication of TLR9. PLoS One 7(9):e45171. [PubMed: 23028824]  [MGI Ref ID J:192006]

Valenzuela DM; Murphy AJ; Frendewey D; Gale NW; Economides AN; Auerbach W; Poueymirou WT; Adams NC; Rojas J; Yasenchak J; Chernomorsky R; Boucher M; Elsasser AL; Esau L; Zheng J; Griffiths JA; Wang X; Su H; Xue Y; Dominguez MG; Noguera I; Torres R; Macdonald LE; Stewart AF; DeChiara TM; Yancopoulos GD. 2003. High-throughput engineering of the mouse genome coupled with high-resolution expression analysis. Nat Biotechnol 21(6):652-9. [PubMed: 12730667]  [MGI Ref ID J:102090]

Volpi C; Fallarino F; Bianchi R; Orabona C; De Luca A; Vacca C; Romani L; Gran B; Grohmann U; Puccetti P; Belladonna ML. 2012. A GpC-rich oligonucleotide acts on plasmacytoid dendritic cells to promote immune suppression. J Immunol 189(5):2283-9. [PubMed: 22844124]  [MGI Ref ID J:189860]

Wei J; Waithman J; Lata R; Mifsud NA; Cebon J; Kay T; Smyth MJ; Sadler AJ; Chen W. 2010. Influenza A infection enhances cross-priming of CD8+ T cells to cell-associated antigens in a TLR7- and type I IFN-dependent fashion. J Immunol 185(10):6013-22. [PubMed: 20956347]  [MGI Ref ID J:165777]

Weiss G; Maaetoft-Udsen K; Stifter SA; Hertzog P; Goriely S; Thomsen AR; Paludan SR; Frokiaer H. 2012. MyD88 drives the IFN-beta response to Lactobacillus acidophilus in dendritic cells through a mechanism involving IRF1, IRF3, and IRF7. J Immunol 189(6):2860-8. [PubMed: 22896628]  [MGI Ref ID J:189947]

Zangi L; Klionsky YZ; Yarimi L; Bachar-Lustig E; Eidelstein Y; Shezen E; Hagin D; Ito Y; Takai T; Reich-Zeliger S; Lask A; Milstein O; Jung S; Shinder V; Reisner Y. 2012. Deletion of cognate CD8 T cells by immature dendritic cells: a novel role for perforin, granzyme A, TREM-1, and TLR7. Blood 120(8):1647-57. [PubMed: 22776817]  [MGI Ref ID J:189175]

Zucchini N; Bessou G; Traub S; Robbins SH; Uematsu S; Akira S; Alexopoulou L; Dalod M. 2008. Cutting edge: Overlapping functions of TLR7 and TLR9 for innate defense against a herpesvirus infection. J Immunol 180(9):5799-803. [PubMed: 18424698]  [MGI Ref ID J:134322]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           MGL375

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, homozygotes may be bred with hemizygotes (X linked).
Mating System	Homozygote x Hemizygote         (Female x Male)   06-DEC-11
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	005304 C57BL/6NJ	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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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"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

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