Strain Name:

B6.129P2-Aim2Gt(CSG445)Byg/J

Stock Number:

013144

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Availability:

Repository- Live

LacZ expression of the Aim2/LacZ fusion protein in macrophages and splenocytes of these mice replaces the endogenous expression of the absent in melanoma 2 gene (Aim2). These mice may be useful for studying the innate immune systems response to bacterial and viral infection.

Description

Strain Information

Former Names B6;129P2-Aim2Gt(CSG445)Byg/J    (Changed: 22-SEP-11 )
B6;129P2-AimGt(CSG445)Byg/J    (Changed: 28-JUL-10 )
Type Congenic; Gene Trap; Mutant Strain;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Mating SystemHomozygote x Homozygote         (Female x Male)   10-JAN-13
Specieslaboratory mouse
GenerationN1+N9F2 (13-DEC-13)
Generation Definitions
 
Donating Investigator Katherine A Fitzgerald,   University of Massachusetts Medical Scho

Description
This secretory trap mutation abolishes Aim2 (endogenous absent in melanoma 2) gene function while expressing an Aim2/LacZ/neo (β-geo) fusion protein. AIM2 is a proinflammatory protein which is a critical part of the inflammasome. LacZ is expressed from the targeted allele in thioglycolate-elicited macrophages (TEMs), bone marrow-derived macrophages (BMDMs), and splenocytes. Homozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These Aim2-/- mice may be useful as a lacZ reporter for AIM2 expression or as a knockout model for studying the innate immune systems response to bacterial and viral infection.

Development
A "secretory trap" targeting vector was used replace the C-terminus of the endogenous absent in melanoma 2 (Aim2) targeted gene with a β-geo fusion protein. This gene trap targeting vector integrated randomly into the Aim2 locus via electroporation into 129P2/OlaHsd-derived E14TG2a.4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts, and chimeric mice were bred with C57BL/6 mice to establish the mutant colony. Upon arrival at The Jackson Laboratory, mice were backcrossed to C57BL/6J (Stock No. 000664) for at least 7 more generations to establish a congenic colony.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Aim2Gt(CSG445)Byg/Aim2Gt(CSG445)Byg

        involves: 129P2/OlaHsd * C57BL/6
  • immune system phenotype
  • abnormal macrophage physiology
    • poly-dA:dT-treated macrophages exhibit less pyrotosis (inflammatory form of cell death) similarly treated wild-type cells   (MGI Ref ID J:158969)
    • however, macrophages respond normally to anthrax lethal toxin, ATP, nigericin, S. typhimurium, or Sendai virus   (MGI Ref ID J:158969)
  • decreased NK cell number
    • mCMV-treated mice exhibit reduced NK cells in the spleen and IFN-gamma producing splenic NK cells compared with similarly treated wild-type mice   (MGI Ref ID J:158969)
  • decreased circulating interleukin-18 level
    • in mCMV-treated mice   (MGI Ref ID J:158969)
  • decreased interleukin-1 beta secretion
    • in response to a synthetic B-form dsDNA (poly-dA:dT), F. tularensis live vaccine strain, L. monocytogenes, mCMV, or Vaccinia Virus, macrophages produce less IL1b than similarly treated wild-type cells   (MGI Ref ID J:158969)
    • however, macrophages treated with HSV-1 exhibit normal IL1beta production   (MGI Ref ID J:158969)
  • decreased interleukin-18 secretion
    • however, macrophages treated with HSV-1 exhibit normal IL1beta production   (MGI Ref ID J:158969)
  • increased interferon-beta secretion
    • synthetic B-form dsDNA (poly-dA:dT)-treated splenocytes and thioglycollate-elicited macrophages produce more IFN-beta than similarly treated wild-type cells   (MGI Ref ID J:158969)
    • however, IFN-beta production by mCMV-treated macrophages is normal   (MGI Ref ID J:158969)
  • increased susceptibility to bacterial infection
    • macrophages treated with F. tularensis live vaccine strain or L. monocytogenes secrete less compared with similarly treated wild-type cells due to impaired inflammasome activation   (MGI Ref ID J:158969)
  • increased susceptibility to viral infection
    • macrophages and bone marrow-derived dendritic cells treated with Vaccinia virus or mCMV produce less IL1b than similarly treated wild-type cells   (MGI Ref ID J:158969)
    • mCMV-treated mice exhibit reduced serum IL18 levels, fewer NK cells in the spleen, fewer IFN-gamma-producing splenic NK cells, and increased viral titers compared with similarly treated wild-type mice   (MGI Ref ID J:158969)
    • however, macrophages treated with HSV-1 exhibit normal IL1beta production and mCMV-treated mice exhibit normal TNF and IFN-beta levels   (MGI Ref ID J:158969)
  • homeostasis/metabolism phenotype
  • decreased circulating interleukin-18 level
    • in mCMV-treated mice   (MGI Ref ID J:158969)
  • hematopoietic system phenotype
  • abnormal macrophage physiology
    • poly-dA:dT-treated macrophages exhibit less pyrotosis (inflammatory form of cell death) similarly treated wild-type cells   (MGI Ref ID J:158969)
    • however, macrophages respond normally to anthrax lethal toxin, ATP, nigericin, S. typhimurium, or Sendai virus   (MGI Ref ID J:158969)
  • decreased NK cell number
    • mCMV-treated mice exhibit reduced NK cells in the spleen and IFN-gamma producing splenic NK cells compared with similarly treated wild-type mice   (MGI Ref ID J:158969)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Aim2Gt(CSG445)Byg/Aim2Gt(CSG445)Byg

        involves: 129P2/OlaHsd
  • immune system phenotype
  • *normal* immune system phenotype
    • mice co-housed with wild-type mice do not affect the susceptibility to induced colitis of wild-type mice   (MGI Ref ID J:173245)
View Research Applications

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

Developmental Biology Research
Internal/Organ Defects
      asplenic

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines
Immunodeficiency
      Macrophage defects

Research Tools
Immunology, Inflammation and Autoimmunity Research
      genes regulating susceptibility to infectious disease and endotoxin

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Aim2Gt(CSG445)Byg
Allele Name gene trap CSG445, BayGenomics
Allele Type Gene trapped
Strain of Origin129P2/OlaHsd
Gene Symbol and Name Aim2, absent in melanoma 2
Chromosome 1
Gene Common Name(s) Gm1313; Ifi210; LOC383619; PYHIN4; gene model 1313, (NCBI);
Molecular Note The beta-geo containing gene trap vector inserted into intron 6. The absence of protein expression was confirmed by western blot analysis on thioglycollate-elicited and bone marrow-derived macrophage extracts. [MGI Ref ID J:158969]

Genotyping

Genotyping Information

Genotyping Protocols

Generic LacZ QPCR, QPCR
Generic LacZ, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Mouse Genome Informatics (MGI) and National Center for Biotechnology Information (NCBI). 2008. Mouse Gene Trap Data Load from dbGSS Database Download :.  [MGI Ref ID J:141210]

Additional References

Aim2Gt(CSG445)Byg related

Belhocine K; Monack DM. 2012. Francisella infection triggers activation of the AIM2 inflammasome in murine dendritic cells. Cell Microbiol 14(1):71-80. [PubMed: 21902795]  [MGI Ref ID J:181382]

Creasey EA; Isberg RR. 2012. The protein SdhA maintains the integrity of the Legionella-containing vacuole. Proc Natl Acad Sci U S A 109(9):3481-6. [PubMed: 22308473]  [MGI Ref ID J:182023]

Elinav E; Strowig T; Kau AL; Henao-Mejia J; Thaiss CA; Booth CJ; Peaper DR; Bertin J; Eisenbarth SC; Gordon JI; Flavell RA. 2011. NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis. Cell 145(5):745-57. [PubMed: 21565393]  [MGI Ref ID J:173245]

Fernandes-Alnemri T; Yu JW; Juliana C; Solorzano L; Kang S; Wu J; Datta P; McCormick M; Huang L; McDermott E; Eisenlohr L; Landel CP; Alnemri ES. 2010. The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat Immunol 11(5):385-93. [PubMed: 20351693]  [MGI Ref ID J:158968]

Ge J; Gong YN; Xu Y; Shao F. 2012. Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation by a Legionella effector functioning in membrane trafficking. Proc Natl Acad Sci U S A 109(16):6193-8. [PubMed: 22474394]  [MGI Ref ID J:183609]

Gomes MT; Campos PC; Oliveira FS; Corsetti PP; Bortoluci KR; Cunha LD; Zamboni DS; Oliveira SC. 2013. Critical Role of ASC Inflammasomes and Bacterial Type IV Secretion System in Caspase-1 Activation and Host Innate Resistance to Brucella abortus Infection. J Immunol 190(7):3629-38. [PubMed: 23460746]  [MGI Ref ID J:194921]

Kalantari P; DeOliveira RB; Chan J; Corbett Y; Rathinam V; Stutz A; Latz E; Gazzinelli RT; Golenbock DT; Fitzgerald KA. 2014. Dual engagement of the NLRP3 and AIM2 inflammasomes by plasmodium-derived hemozoin and DNA during malaria. Cell Rep 6(1):196-210. [PubMed: 24388751]  [MGI Ref ID J:206874]

Nakahira K; Haspel JA; Rathinam VA; Lee SJ; Dolinay T; Lam HC; Englert JA; Rabinovitch M; Cernadas M; Kim HP; Fitzgerald KA; Ryter SW; Choi AM. 2011. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 12(3):222-30. [PubMed: 21151103]  [MGI Ref ID J:169252]

Panchanathan R; Duan X; Shen H; Rathinam VA; Erickson LD; Fitzgerald KA; Choubey D. 2010. Aim2 deficiency stimulates the expression of IFN-inducible Ifi202, a lupus susceptibility murine gene within the Nba2 autoimmune susceptibility locus. J Immunol 185(12):7385-93. [PubMed: 21057088]  [MGI Ref ID J:167482]

Panchanathan R; Liu H; Liu H; Fang CM; Erickson LD; Pitha PM; Choubey D. 2012. Distinct regulation of murine lupus susceptibility genes by the IRF5/Blimp-1 axis. J Immunol 188(1):270-8. [PubMed: 22116829]  [MGI Ref ID J:180587]

Panchanathan R; Shen H; Duan X; Rathinam VA; Erickson LD; Fitzgerald KA; Choubey D. 2011. Aim2 deficiency in mice suppresses the expression of the inhibitory Fcgamma receptor (FcgammaRIIB) through the induction of the IFN-inducible p202, a lupus susceptibility protein. J Immunol 186(12):6762-70. [PubMed: 21551362]  [MGI Ref ID J:175498]

Rathinam VA; Jiang Z; Waggoner SN; Sharma S; Cole LE; Waggoner L; Vanaja SK; Monks BG; Ganesan S; Latz E; Hornung V; Vogel SN; Szomolanyi-Tsuda E; Fitzgerald KA. 2010. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat Immunol 11(5):395-402. [PubMed: 20351692]  [MGI Ref ID J:158969]

Shah S; Bohsali A; Ahlbrand SE; Srinivasan L; Rathinam VA; Vogel SN; Fitzgerald KA; Sutterwala FS; Briken V. 2013. Cutting edge: Mycobacterium tuberculosis but not nonvirulent mycobacteria inhibits IFN-beta and AIM2 inflammasome-dependent IL-1beta production via its ESX-1 secretion system. J Immunol 191(7):3514-8. [PubMed: 23997220]  [MGI Ref ID J:205949]

Shi CS; Shenderov K; Huang NN; Kabat J; Abu-Asab M; Fitzgerald KA; Sher A; Kehrl JH. 2012. Activation of autophagy by inflammatory signals limits IL-1beta production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol 13(3):255-63. [PubMed: 22286270]  [MGI Ref ID J:181253]

Shimada K; Crother TR; Karlin J; Dagvadorj J; Chiba N; Chen S; Ramanujan VK; Wolf AJ; Vergnes L; Ojcius DM; Rentsendorj A; Vargas M; Guerrero C; Wang Y; Fitzgerald KA; Underhill DM; Town T; Arditi M. 2012. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 36(3):401-14. [PubMed: 22342844]  [MGI Ref ID J:187340]

Stryke D; Kawamoto M; Huang CC; Johns SJ; King LA; Harper CA; Meng EC; Lee RE; Yee A; L'Italien L; Chuang PT; Young SG; Skarnes WC; Babbitt PC; Ferrin TE. 2003. BayGenomics: a resource of insertional mutations in mouse embryonic stem cells. Nucleic Acids Res 31(1):278-81. [PubMed: 12520002]  [MGI Ref ID J:91812]

Ulland TK; Janowski AM; Buchan BW; Faron M; Cassel SL; Jones BD; Sutterwala FS. 2013. Francisella tularensis Live Vaccine Strain Folate Metabolism and Pseudouridine Synthase Gene Mutants Modulate Macrophage Caspase-1 Activation. Infect Immun 81(1):201-8. [PubMed: 23115038]  [MGI Ref ID J:190664]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           MGL375

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.
Mating SystemHomozygote x Homozygote         (Female x Male)   10-JAN-13
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 $232.00Female or MaleHomozygous for Aim2Gt(CSG445)Byg  
Price per Pair (US dollars $)Pair Genotype
$464.00Homozygous for Aim2Gt(CSG445)Byg x Homozygous for Aim2Gt(CSG445)Byg  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHomozygous for Aim2Gt(CSG445)Byg  
Price per Pair (US dollars $)Pair Genotype
$603.20Homozygous for Aim2Gt(CSG445)Byg x Homozygous for Aim2Gt(CSG445)Byg  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Control Information

  Control
   000664 C57BL/6J (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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