Description

Strain Information

Former Names B6;129-D430028G21Riktm1Zjc/J    (Changed: 16-APR-09 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   08-NOV-11 Species laboratory mouse Generation F?+F5 (16-OCT-12) Generation Definitions   Donating Investigator Zhijian 'James' Chen,   UT Southwestern; HHMI

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. Loss of MAVS (mitochondrial antiviral signaling) protein expression abolishes viral induction of interferons and prevents the activation of NFΚB (Rela, v-rel reticuloendotheliosis viral oncogene homolog A (avian)) and IRF3 (interferon regulatory factor 3) in multiple cell types, except plasmacytoid dendritic cells (pDCs). The protein is not required for interferon induction by cytosolic DNA or by Listeria monocytogenes. Mice lacking the protein fail to induce interferons in response to poly(I:C) stimulation and are severely compromised in immune defense against viral infection. Experimental results provide in vivo evidence that the cytosolic viral signaling pathway through the targeted gene is specifically required for innate immune responses against viral infection.

Development
A segment of exon 2 (starting at the ATG start codon) and exon 3 were replaced with a PGK-neomycin resistance cassette flanked by loxP sites. A 129-derived embryonic stem cell line was used to create the mutation. Germline chimaera's were bred to C57BL/6. This strain was maintained on a mixed C57BL/6 and 129SvEv genetic background by the donating laboratory.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Mavs^tm1Zjc/Mavs⁺

        involves: 129/Sv * C57BL/6

• immune system phenotype
• abnormal innate immunity
  • intermediate levels of IFNalpha, IFNbeta and Il-6 are found in the sera of heterozygotes after injection of poly(I:C)   (MGI Ref ID J:110905)
• increased susceptibility to viral infection
  • all heterozygotes die within 4 days of infection with VSV (vesicular stomatitis virus) while wild-type survive; with infection by 2 x 10⁸ of the less virulent VSV-GFP, 2/5 heterozygotes survive 8 days while 5/7 wild-type survive 12 days and infection with half the viral titer, 3 out of 4 survive past 12 days   (MGI Ref ID J:110905)

Mavs^tm1Zjc/Mavs^tm1Zjc

        involves: 129/Sv * C57BL/6

• immune system phenotype
• abnormal dendritic cell physiology
  • interferon induction in conventional dendritic cells when stimulated with Sendai virus; plasmacytoid dendritic cells show normal interferon levels in response viral infection and LPS response is normal in both types of dendritic cells   (MGI Ref ID J:110905)
• abnormal innate immunity
  • MEFs from mutant mice display impaired innate immunity when infected with Sendai virus; interferon production and Il-6 production is defective; Il-6 induction is normal however when mice are stimulated with LPS   (MGI Ref ID J:110905)
  • induction of interferon alpha and beta (Ifna, Ifnb respectively) is abolished in the first 4 hours after injection of poly(I:C) and production of Il-6 is impaired in this period; there is a late induction of Il-6 at reduced levels after 4 hours   (MGI Ref ID J:110905)
• • abnormal macrophage physiology
    • isolated bone-marrow derived and peripheral macrophages do not show induction of IFNalpha, IFNbeta, and Il-6 or activation of NF-kappaB by Sendai virus; response to LPS is normal though   (MGI Ref ID J:110905)
• increased susceptibility to viral infection
  • all homozygotes (and heterozygotes) die within 4 days of infection with VSV (vesicular stomatitis virus) while wild-type survive; with infection by 2 x 10⁸ of the less virulent VSV-GFP, all homozygotes die within 8 days while 5/7 wild-type survive 12 days and infection with _ the viral titer, 50% of homozygotes survive to day 12   (MGI Ref ID J:110905)

View Research Applications

Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Intracellular Signaling Molecules

Virology Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Mavstm1Zjc
Allele Name		targeted mutation 1, Zhijian J Chen
Allele Type		Targeted (knock-out)
Common Name(s)		Mavs-;
Mutation Made By		Zhijian 'James' Chen,   UT Southwestern; HHMI
Gene Symbol and Name		Mavs, mitochondrial antiviral signaling protein
Chromosome		2
Gene Common Name(s)		CARDIF; D430028G21Rik; IPS-1; IPS1; RIKEN cDNA D430028G21 gene; VISA;
Molecular Note		Sequence beginning at the ATG in exon 2 and extending through exon 3 was replaced with a floxed neomycin resistance gene. Immunoblot failed to detect protein in mutants. [MGI Ref ID J:110905]

Genotyping

Genotyping Information

Genotyping Protocols

Mavs^tm1Zjc, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Sun Q; Sun L; Liu HH; Chen X; Seth RB; Forman J; Chen ZJ. 2006. The specific and essential role of MAVS in antiviral innate immune responses. Immunity 24(5):633-42. [PubMed: 16713980]  [MGI Ref ID J:110905]

Additional References

Mavs^tm1Zjc related

Bhoj VG; Sun Q; Bhoj EJ; Somers C; Chen X; Torres JP; Mejias A; Gomez AM; Jafri H; Ramilo O; Chen ZJ. 2008. MAVS and MyD88 are essential for innate immunity but not cytotoxic T lymphocyte response against respiratory syncytial virus. Proc Natl Acad Sci U S A 105(37):14046-51. [PubMed: 18780793]  [MGI Ref ID J:139074]

Broquet AH; Hirata Y; McAllister CS; Kagnoff MF. 2011. RIG-I/MDA5/MAVS are required to signal a protective IFN response in rotavirus-infected intestinal epithelium. J Immunol 186(3):1618-26. [PubMed: 21187438]  [MGI Ref ID J:168914]

Chen H; Sun H; You F; Sun W; Zhou X; Chen L; Yang J; Wang Y; Tang H; Guan Y; Xia W; Gu J; Ishikawa H; Gutman D; Barber G; Qin Z; Jiang Z. 2011. Activation of STAT6 by STING Is Critical for Antiviral Innate Immunity. Cell 147(2):436-46. [PubMed: 22000020]  [MGI Ref ID J:177502]

Chessler AD; Ferreira LR; Chang TH; Fitzgerald KA; Burleigh BA. 2008. A novel IFN regulatory factor 3-dependent pathway activated by trypanosomes triggers IFN-beta in macrophages and fibroblasts. J Immunol 181(11):7917-24. [PubMed: 19017982]  [MGI Ref ID J:142378]

Clingan JM; Ostrow K; Hosiawa KA; Chen ZJ; Matloubian M. 2012. Differential roles for RIG-I-like receptors and nucleic acid-sensing TLR pathways in controlling a chronic viral infection. J Immunol 188(9):4432-40. [PubMed: 22447976]  [MGI Ref ID J:188395]

Cotter CR; Kim WK; Nguyen ML; Yount JS; Lopez CB; Blaho JA; Moran TM. 2011. The virion host shutoff protein of herpes simplex virus 1 blocks the replication-independent activation of NF-kappaB in dendritic cells in the absence of type I interferon signaling. J Virol 85(23):12662-72. [PubMed: 21937652]  [MGI Ref ID J:178555]

Goutagny N; Jiang Z; Tian J; Parroche P; Schickli J; Monks BG; Ulbrandt N; Ji H; Kiener PA; Coyle AJ; Fitzgerald KA. 2010. Cell type-specific recognition of human metapneumoviruses (HMPVs) by retinoic acid-inducible gene I (RIG-I) and TLR7 and viral interference of RIG-I ligand recognition by HMPV-B1 phosphoprotein. J Immunol 184(3):1168-79. [PubMed: 20042593]  [MGI Ref ID J:159497]

Henry T; Brotcke A; Weiss DS; Thompson LJ; Monack DM. 2007. Type I interferon signaling is required for activation of the inflammasome during Francisella infection. J Exp Med 204(5):987-94. [PubMed: 17452523]  [MGI Ref ID J:125737]

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]

Kang MJ; Lee CG; Lee JY; Dela Cruz CS; Chen ZJ; Enelow R; Elias JA. 2008. Cigarette smoke selectively enhances viral PAMP- and virus-induced pulmonary innate immune and remodeling responses in mice. J Clin Invest 118(8):2771-84. [PubMed: 18654661]  [MGI Ref ID J:140864]

Li XD; Chiu YH; Ismail AS; Behrendt CL; Wight-Carter M; Hooper LV; Chen ZJ. 2011. Mitochondrial antiviral signaling protein (MAVS) monitors commensal bacteria and induces an immune response that prevents experimental colitis. Proc Natl Acad Sci U S A 108(42):17390-5. [PubMed: 21960441]  [MGI Ref ID J:177458]

McWhirter SM; Barbalat R; Monroe KM; Fontana MF; Hyodo M; Joncker NT; Ishii KJ; Akira S; Colonna M; Chen ZJ; Fitzgerald KA; Hayakawa Y; Vance RE. 2009. A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP. J Exp Med 206(9):1899-911. [PubMed: 19652017]  [MGI Ref ID J:152182]

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]

Sharma S; Deoliveira RB; Kalantari P; Parroche P; Goutagny N; Jiang Z; Chan J; Bartholomeu DC; Lauw F; Hall JP; Barber GN; Gazzinelli RT; Fitzgerald KA; Golenbock DT. 2011. Innate Immune Recognition of an AT-Rich Stem-Loop DNA Motif in the Plasmodium falciparum Genome. Immunity 35(2):194-207. [PubMed: 21820332]  [MGI Ref ID J:175845]

Siednienko J; Gajanayake T; Fitzgerald KA; Moynagh P; Miggin SM. 2011. Absence of MyD88 results in enhanced TLR3-dependent phosphorylation of IRF3 and increased IFN-(beta) and RANTES production. J Immunol 186(4):2514-22. [PubMed: 21248248]  [MGI Ref ID J:169149]

Tarallo V; Hirano Y; Gelfand BD; Dridi S; Kerur N; Kim Y; Cho WG; Kaneko H; Fowler BJ; Bogdanovich S; Albuquerque RJ; Hauswirth WW; Chiodo VA; Kugel JF; Goodrich JA; Ponicsan SL; Chaudhuri G; Murphy MP; Dunaief JL; Ambati BK; Ogura Y; Yoo JW; Lee DK; Provost P; Hinton DR; Nunez G; Baffi JZ; Kleinman ME; Ambati J. 2012. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell 149(4):847-59. [PubMed: 22541070]  [MGI Ref ID J:186198]

Wang F; Xia W; Liu F; Li J; Wang G; Gu J. 2012. Interferon regulator factor 1/retinoic inducible gene I (IRF1/RIG-I) axis mediates 25-hydroxycholesterol-induced interleukin-8 production in atherosclerosis. Cardiovasc Res 93(1):190-9. [PubMed: 21979142]  [MGI Ref ID J:194880]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, heterozygotes or homozygotes may be bred.
Mating System	Homozygote x Homozygote         (Female x Male)   08-NOV-11
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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