Strain Name:

B6;129-Mavstm1Zjc/J

Stock Number:

008634

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Availability:

Repository- Live

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Loss of MAVS (mitochondrial antiviral signaling) protein expression in this knock-out strain abolishes viral induction of interferons and prevents the activation of NFΚB and IRF3 in multiple cell types, except plasmacytoid dendritic cells. 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.

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.
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Mating SystemHomozygote x Homozygote         (Female x Male)   08-NOV-11
Specieslaboratory mouse
GenerationF?+F7 (11-DEC-13)
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

Mavstm1Zjc/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)

Mavstm1Zjc/Mavstm1Zjc

        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)
  • hematopoietic system phenotype
  • 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)
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 (Null/Knockout)
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

Mavstm1Zjc, 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

Mavstm1Zjc 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]

Ermler ME; Yerukhim E; Schriewer J; Schattgen S; Traylor Z; Wespiser AR; Caffrey DR; Chen ZJ; King CH; Gale M Jr; Colonna M; Fitzgerald KA; Buller RM; Hise AG. 2013. RNA helicase signaling is critical for type i interferon production and protection against Rift Valley fever virus during mucosal challenge. J Virol 87(9):4846-60. [PubMed: 23408632]  [MGI Ref ID J:197207]

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]

Guan K; Zheng Z; Song T; He X; Xu C; Zhang Y; Ma S; Wang Y; Xu Q; Cao Y; Li J; Yang X; Ge X; Wei C; Zhong H. 2013. MAVS regulates apoptotic cell death by decreasing K48-linked ubiquitination of voltage-dependent anion channel 1. Mol Cell Biol 33(16):3137-49. [PubMed: 23754752]  [MGI Ref ID J:204562]

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]

Liu S; Chen J; Cai X; Wu J; Chen X; Wu YT; Sun L; Chen ZJ. 2013. MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades. Elife 2:e00785. [PubMed: 23951545]  [MGI Ref ID J:207797]

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]

Mukherjee P; Woods TA; Moore RA; Peterson KE. 2013. Activation of the Innate Signaling Molecule MAVS by Bunyavirus Infection Upregulates the Adaptor Protein SARM1, Leading to Neuronal Death. Immunity 38(4):705-16. [PubMed: 23499490]  [MGI Ref ID J:196200]

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]

Pang IK; Pillai PS; Iwasaki A. 2013. Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I. Proc Natl Acad Sci U S A 110(34):13910-5. [PubMed: 23918369]  [MGI Ref ID J:200675]

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]

Subramanian N; Natarajan K; Clatworthy MR; Wang Z; Germain RN. 2013. The adaptor MAVS promotes NLRP3 mitochondrial localization and inflammasome activation. Cell 153(2):348-61. [PubMed: 23582325]  [MGI Ref ID J:197368]

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]

Weinlich R; Oberst A; Dillon CP; Janke LJ; Milasta S; Lukens JR; Rodriguez DA; Gurung P; Savage C; Kanneganti TD; Green DR. 2013. Protective roles for caspase-8 and cFLIP in adult homeostasis. Cell Rep 5(2):340-8. [PubMed: 24095739]  [MGI Ref ID J:203778]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

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

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $199.90Female or MaleHomozygous for Mavstm1Zjc  
Price per Pair (US dollars $)Pair Genotype
$399.80Homozygous for Mavstm1Zjc x Homozygous for Mavstm1Zjc  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $259.90Female or MaleHomozygous for Mavstm1Zjc  
Price per Pair (US dollars $)Pair Genotype
$519.80Homozygous for Mavstm1Zjc x Homozygous for Mavstm1Zjc  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

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

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