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. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   10-JAN-13 Species laboratory mouse Generation N1+N9 (01-NOV-11) 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

Aim2^{Gt(CSG445)Byg}/Aim2^{Gt(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
• 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 may relate to a genetic background differing from this JAX^® Mice strain.

Aim2^{Gt(CSG445)Byg}/Aim2^{Gt(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 and Inflammation 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 Origin		129P2/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

Aim2^{Gt(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]

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]

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           MGL377

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   10-JAN-13
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

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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