Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; 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)   01-MAR-06 Species laboratory mouse Generation N10F11N1F1 (22-JAN-09) Generation Definitions   Donating Investigator Shizuo Akira,   Research Institute for Microbial Disease

Description
Mice that are homozygous null for the Il18 gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Il18 gene product (mRNA or protein) is detected. Homozygous null mice exhibit reduced levels of interferon gamma in response to heat killed bacteria and lipopolysaccharide. IL-12 levels in the serum are similar to wild type after LPS challenge, indicating that the decreased interferon gamma response in Il18 deficient mice is not due to low induction of IL-12. Il18 deficient mice also exhibit diminished natural killer cell activity and impaired T helper lymphocyte response.

Development
A targeting vector containing neomycin resistance and Herpes simplex virus thymidine kinase genes was used to disrupt exons 3-5. The construct was transfected into 129P2/OlaHsd-derived E14-1 embryonic stem cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Il18^tm1Aki/Il18^tm1Aki

        B6.129P2-Il18^tm1Aki

• immune system phenotype
• impaired neutrophil chemotaxis
  • less numbers of neutrophils are recruited to the lung both 6- and 24 hours after infection with Haemophilus influenzae   (MGI Ref ID J:125285)
• increased susceptibility to bacterial infection
  • bacterial counts in the lung are 20-fold higher one day after infection with Haemophilus influenzae   (MGI Ref ID J:125285)
  • there is less inflammation present in the lungs 6- and 24- hours after infection with histological scores significantly reduced compared to wild-type mice   (MGI Ref ID J:125285)
  • mice are able to clear infection from the lungs 10 days after infection, which is similar to wild-type mice   (MGI Ref ID J:125285)
• increased susceptibility to induced colitis
  • mice exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis compared with similarly treated wild-type mice   (MGI Ref ID J:173245)
  • mice transmit increased susceptibility to DSS-induced colitis to co-housed wild-type mice   (MGI Ref ID J:173245)
• digestive/alimentary phenotype
• abnormal gut flora balance
  • mice and co-housed wild-type mice exhibit expanded bacterial phylotypes compared with wild-type mice   (MGI Ref ID J:173245)
• increased susceptibility to induced colitis
  • mice exhibit increased susceptibility to dextran sodium sulfate (DSS)-induced colitis compared with similarly treated wild-type mice   (MGI Ref ID J:173245)
  • mice transmit increased susceptibility to DSS-induced colitis to co-housed wild-type mice   (MGI Ref ID J:173245)
• cellular phenotype
• impaired neutrophil chemotaxis
  • less numbers of neutrophils are recruited to the lung both 6- and 24 hours after infection with Haemophilus influenzae   (MGI Ref ID J:125285)

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

Il18^tm1Aki/Il18⁺

        involves: 129P2/OlaHsd

• behavior/neurological phenotype
• polyphagia
  • female mice overeat chow relative to wild-type mice during the last 6 hours of night and the first three hours in the day but not to the degree observed in Il18^tm1Aki homozygotes   (MGI Ref ID J:122588)

Il18^tm1Aki/Il18^tm1Aki

        involves: 129P2/OlaHsd

• immune system phenotype
• abnormal T-helper 1 physiology
  • in vivo Th1 cell response is impaired as indicated by the low amounts of IFN-gamma produced by T cells in response to P. acnes or M. bovis antigens   (MGI Ref ID J:46514)
  • in vitro differentiation of Th1 T cells by culturing in the presence of IL-12 is normal   (MGI Ref ID J:46514)
• abnormal macrophage physiology
  • macrophages are resistant to cytotoxicity by SP1^- Salmonella   (MGI Ref ID J:112400)
• decreased circulating interferon-gamma level
  • serum IFN-gamma levels are 1/5^th of wild-type levels 6 hours after treatment with LPS in mice sensitized to Prionibacterium acnes (P. acnes)   (MGI Ref ID J:46514)
• decreased circulating interleukin-18 level
  • IL-18 is absent in the serum before and after LPS injection   (MGI Ref ID J:46514)
  • IL-18 was undetectable in the sera of mice   (MGI Ref ID J:122588)
• decreased interferon-gamma secretion
  • splenic T cells produce about 1/10^th the amount of IFN-gamma as T cells from wild-type mice 7 days after injection with heat killed P. acnes   (MGI Ref ID J:46514)
• impaired natural killer cell mediated cytotoxicity
  • the killing activity of splenic NK cells is about 1/3^rd that of wild-type mice as measured by in vitro co-culturing with YAC-1 target cells   (MGI Ref ID J:46514)
  • normal level of target cell killing can be restored by in vivo administration of IL-18 for two days   (MGI Ref ID J:46514)
  • target cell killing can also be restored by in vivo pre-treatment with high amounts of IL-12 or the addition of small amounts of IL-12 to the co-culture   (MGI Ref ID J:46514)
• increased susceptibility to bacterial infection
  • mice succumb more rapidly than controls to 10⁸ CFU of Salmonella with a median survival time of 6 days compared to 8 days for controls   (MGI Ref ID J:112400)
  • there is an average 30-fold-higher bacterial loads in infected Peyer's patches, mesenteric lymph nodes, and spleens than in the infected organs of wild-type animals   (MGI Ref ID J:112400)
• growth/size phenotype
• increased susceptibility to age related obesity
  • female mice have a greater body weight gain during the 5^th month of life than controls going from 1% greater mean body weight at 4 months of age to 27% greater mean body weight at 5 months of age   (MGI Ref ID J:122588)
  • male mice have a 2-fold greater weight gain between 4 and 7 months of age with mean body weight being 14% higher by 27 weeks of age compared to controls   (MGI Ref ID J:122588)
• adipose tissue phenotype
• increased percent body fat
  • weight gain is mostly due to increases in white fat resulting in a percent body fats that exceed 20% for mice 30 weeks in age   (MGI Ref ID J:122588)
• increased total fat pad weight
  • white fat pads are heavier on both absolute and relative scales with the largest increases occurring in the inguinal and gonadal pads where weights were 1 gram larger compared to controls   (MGI Ref ID J:122588)
• increased white adipose tissue amount
  • the collective white fat pad mass of these mice is 2-3 fold greater that of wild-type mice   (MGI Ref ID J:122588)
• homeostasis/metabolism phenotype
• decreased circulating interferon-gamma level
  • serum IFN-gamma levels are 1/5^th of wild-type levels 6 hours after treatment with LPS in mice sensitized to Prionibacterium acnes (P. acnes)   (MGI Ref ID J:46514)
• decreased circulating interleukin-18 level
  • IL-18 is absent in the serum before and after LPS injection   (MGI Ref ID J:46514)
  • IL-18 was undetectable in the sera of mice   (MGI Ref ID J:122588)
• decreased energy expenditure
  • mice gain 2- to 3-fold more body weight than controls per unit body weight consumed   (MGI Ref ID J:122588)
  • female mice have stably reduced oxygen consumption along with decreased carbon dioxide and heat production   (MGI Ref ID J:122588)
• decreased oxygen consumption
  • female mice have stably reduced oxygen consumption along with decreased carbon dioxide   (MGI Ref ID J:122588)
  • the respiratory exchange ratio (VCO-2/ VO-2) is increased in both female and male mice early in the dark cycle   (MGI Ref ID J:122588)
• behavior/neurological phenotype
• polyphagia
  • hyperphagia is seen at 15 weeks of age before changes in body weight are observed   (MGI Ref ID J:122588)
  • overeating of chow increases later in adulthood for both female and male mice even when comsumption is normalized to bodyweight   (MGI Ref ID J:122588)
  • hyperphagia varied according to the time of day with increase consumption occurring during the last six hours of the dark cycle and the first three hours of the light cycle   (MGI Ref ID J:122588)
  • during this period of the daily cycle mice will eat twice as much as controls   (MGI Ref ID J:122588)
  • hyperphagia also occurs on a low fat diet but not on a high fat diet when consumption is normalized to bodyweight   (MGI Ref ID J:122588)

Il18^tm1Aki/Il18^tm1Aki

        involves: 129P2/OlaHsd * C57BL/6

• vision/eye phenotype
• abnormal retinal vasculature morphology
  • mice 7 days of age display angiectasis and vascular leakage in the mid-periphery of the retina   (MGI Ref ID J:92254)
  • mice 14 days of age have areas of the retina that are not perfused with capillaries   (MGI Ref ID J:92254)
  • abnormal blood vessels are found in the vitreous outside of the inner-limiting membrane in young mice   (MGI Ref ID J:92254)
  • other blood vessels in the retina of young mice have a tortured appearance   (MGI Ref ID J:92254)
  • vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age   (MGI Ref ID J:92254)
• retinal hemorrhage
  • vascular leakage is observed in the retinas of mice starting at 7 days of age   (MGI Ref ID J:92254)
  • vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age   (MGI Ref ID J:92254)
• cardiovascular system phenotype
• abnormal heart left ventricle morphology
  • the left ventricular volume of 3-4 month old mice is reduced   (MGI Ref ID J:118183)
  • hypertrophic growth of the left ventricle induced by pressure overload is significantly reduced compared to wild-type controls   (MGI Ref ID J:118183)
  • end diastolic volumes increased in response to pressure overload compared to wild-type mice that have decreased diastolic volumes   (MGI Ref ID J:118183)
• abnormal retinal vasculature morphology
  • mice 7 days of age display angiectasis and vascular leakage in the mid-periphery of the retina   (MGI Ref ID J:92254)
  • mice 14 days of age have areas of the retina that are not perfused with capillaries   (MGI Ref ID J:92254)
  • abnormal blood vessels are found in the vitreous outside of the inner-limiting membrane in young mice   (MGI Ref ID J:92254)
  • other blood vessels in the retina of young mice have a tortured appearance   (MGI Ref ID J:92254)
  • vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age   (MGI Ref ID J:92254)
• decreased ventricle muscle contractility
  • left ventricle contractility decreased in response to pressure overload compared to the increases observed in wild-type mice   (MGI Ref ID J:118183)
• retinal hemorrhage
  • vascular leakage is observed in the retinas of mice starting at 7 days of age   (MGI Ref ID J:92254)
  • vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age   (MGI Ref ID J:92254)
• hematopoietic system phenotype
• abnormal microglial cell morphology
  • stress-induced increase in microglial cell surface, which is a marker of activation, is significantly reduced by 1.5 to 3 fold in these mice   (MGI Ref ID J:122031)
• immune system phenotype
• abnormal microglial cell morphology
  • stress-induced increase in microglial cell surface, which is a marker of activation, is significantly reduced by 1.5 to 3 fold in these mice   (MGI Ref ID J:122031)
• nervous system phenotype
• abnormal microglial cell morphology
  • stress-induced increase in microglial cell surface, which is a marker of activation, is significantly reduced by 1.5 to 3 fold in these mice   (MGI Ref ID J:122031)
• decreased cerebral infarction size
  • the total volume of infarction caused by hypoxia-ischemia (HI) was reduced from 53% in wild-type mice to 42% in these mice   (MGI Ref ID J:124249)
  • the neuropathological scores to measure brain injury resulting from HI were reduced with the most marked reduction of 35% occurring in the cerebral cortex   (MGI Ref ID J:124249)
• homeostasis/metabolism phenotype
• decreased cerebral infarction size
  • the total volume of infarction caused by hypoxia-ischemia (HI) was reduced from 53% in wild-type mice to 42% in these mice   (MGI Ref ID J:124249)
  • the neuropathological scores to measure brain injury resulting from HI were reduced with the most marked reduction of 35% occurring in the cerebral cortex   (MGI Ref ID J:124249)
• muscle phenotype
• decreased ventricle muscle contractility
  • left ventricle contractility decreased in response to pressure overload compared to the increases observed in wild-type mice   (MGI Ref ID J:118183)

Il18^tm1Aki/Il18^tm1Aki

        C.129P2-Il18^tm1Aki

• digestive/alimentary phenotype
• gastrointestinal hemorrhage
  • there is less bleeding associated with stress-induced ulcers in the stomach with bleeding index scores being about half that of wild-type mice   (MGI Ref ID J:120594)
• hyperchlorhydria
  • there is decreased secretion of gastric acid in the stomach 1- and 2- hours after stress induction compared to wild-type mice   (MGI Ref ID J:120594)
• stomach inflammation
  • histidine decarboxylase activity in the stomachof untreated mice is significantly lower than in wild-type mice   (MGI Ref ID J:120594)
  • histamine concentrations in the gastric mucosa 1- and 2- hours after stress induction are 2-fold lower than in wild-type mice   (MGI Ref ID J:120594)
• cardiovascular system phenotype
• gastrointestinal hemorrhage
  • there is less bleeding associated with stress-induced ulcers in the stomach with bleeding index scores being about half that of wild-type mice   (MGI Ref ID J:120594)
• immune system phenotype
• stomach inflammation
  • histidine decarboxylase activity in the stomachof untreated mice is significantly lower than in wild-type mice   (MGI Ref ID J:120594)
  • histamine concentrations in the gastric mucosa 1- and 2- hours after stress induction are 2-fold lower than in wild-type mice   (MGI Ref ID J:120594)

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Research Applications

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

Il18^tm1Aki related

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines
Immunodeficiency
      NK Cell Deficiency
Inflammation

Research Tools
Immunology and Inflammation Research
      NK Cell Deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Il18tm1Aki
Allele Name		targeted mutation 1, Shizuo Akira
Allele Type		Targeted (knock-out)
Common Name(s)		IL-18; IL-18-; Il18-;
Mutation Made By		Shizuo Akira,   Research Institute for Microbial Disease
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14.1
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Il18, interleukin 18
Chromosome		9
Gene Common Name(s)		IGIF; IL-18; IL-1g; IL1F4; Igif; interferon gamma inducing factor;
Molecular Note		Replacement of exons 3, 4 and 5 with a neomycin resistance gene inserted in frame into exon 3. By Northern blot analysis, mRNA could not be detected in macrophages derived from homozygous mutant mice. By ELISA assay, protein cound not be detected in serum of homozygous mutant mice after intravenous injection of lipopolysaccharide. [MGI Ref ID J:46514]

Genotyping

Genotyping Information

Genotyping Protocols

Il18^tm1Aki, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Takeda K; Tsutsui H; Yoshimoto T; Adachi O; Yoshida N; Kishimoto T ; Okamura H ; Nakanishi K ; Akira S. 1998. Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity 8(3):383-90. [PubMed: 9529155]  [MGI Ref ID J:46514]

Additional References

Il18^tm1Aki related

Aachoui Y; Leaf IA; Hagar JA; Fontana MF; Campos CG; Zak DE; Tan MH; Cotter PA; Vance RE; Aderem A; Miao EA. 2013. Caspase-11 protects against bacteria that escape the vacuole. Science 339(6122):975-8. [PubMed: 23348507]  [MGI Ref ID J:193387]

Adachi K; Tsutsui H; Kashiwamura S; Seki E; Nakano H; Takeuchi O; Takeda K; Okumura K; Van Kaer L; Okamura H; Akira S; Nakanishi K. 2001. Plasmodium berghei infection in mice induces liver injury by an IL-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism. J Immunol 167(10):5928-34. [PubMed: 11698470]  [MGI Ref ID J:118004]

Akhiani AA; Schon K; Lycke N. 2004. Vaccine-induced immunity against Helicobacter pylori infection is impaired in IL-18-deficient mice. J Immunol 173(5):3348-56. [PubMed: 15322198]  [MGI Ref ID J:92673]

Andoh T; Kishi H; Motoki K; Nakanishi K; Kuraishi Y; Muraguchi A. 2008. Protective effect of IL-18 on kainate- and IL-1beta-induced cerebellar ataxia in mice. J Immunol 180(4):2322-8. [PubMed: 18250441]  [MGI Ref ID J:131996]

Andoniou CE; van Dommelen SL; Voigt V; Andrews DM; Brizard G; Asselin-Paturel C; Delale T; Stacey KJ; Trinchieri G; Degli-Esposti MA. 2005. Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity. Nat Immunol 6(10):1011-9. [PubMed: 16142239]  [MGI Ref ID J:110194]

Ariga H; Shimohakamada Y; Nakada M; Tokunaga T; Kikuchi T; Kariyone A; Tamura T; Takatsu K. 2007. Instruction of naive CD4+ T-cell fate to T-bet expression and T helper 1 development: roles of T-cell receptor-mediated signals. Immunology 122(2):210-21. [PubMed: 17490433]  [MGI Ref ID J:125688]

Barquero-Calvo E; Chaves-Olarte E; Weiss DS; Guzman-Verri C; Chacon-Diaz C; Rucavado A; Moriyon I; Moreno E. 2007. Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection. PLoS ONE 2(7):e631. [PubMed: 17637846]  [MGI Ref ID J:129323]

Barr DP; Belz GT; Reading PC; Wojtasiak M; Whitney PG; Heath WR; Carbone FR; Brooks AG. 2007. A role for plasmacytoid dendritic cells in the rapid IL-18-dependent activation of NK cells following HSV-1 infection. Eur J Immunol 37(5):1334-42. [PubMed: 17407097]  [MGI Ref ID J:123560]

Behera AK; Hildebrand E; Bronson RT; Perides G; Uematsu S; Akira S; Hu LT. 2006. MyD88 deficiency results in tissue-specific changes in cytokine induction and inflammation in interleukin-18-independent mice infected with Borrelia burgdorferi. Infect Immun 74(3):1462-70. [PubMed: 16495516]  [MGI Ref ID J:107422]

Brigl M; Tatituri RV; Watts GF; Bhowruth V; Leadbetter EA; Barton N; Cohen NR; Hsu FF; Besra GS; Brenner MB. 2011. Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection. J Exp Med 208(6):1163-77. [PubMed: 21555485]  [MGI Ref ID J:177293]

Burt BM; Plitas G; Stableford JA; Nguyen HM; Bamboat ZM; Pillarisetty VG; DeMatteo RP. 2008. CD11c identifies a subset of murine liver natural killer cells that responds to adenoviral hepatitis. J Leukoc Biol 84(4):1039-46. [PubMed: 18664530]  [MGI Ref ID J:140218]

Cataisson C; Salcedo R; Hakim S; Moffitt BA; Wright L; Yi M; Stephens R; Dai RM; Lyakh L; Schenten D; Yuspa HS; Trinchieri G. 2012. IL-1R-MyD88 signaling in keratinocyte transformation and carcinogenesis. J Exp Med 209(9):1689-702. [PubMed: 22908325]  [MGI Ref ID J:191813]

Ceballos-Olvera I; Sahoo M; Miller MA; Del Barrio L; Re F. 2011. Inflammasome-dependent pyroptosis and IL-18 protect against Burkholderia pseudomallei lung infection while IL-1beta is deleterious. PLoS Pathog 7(12):e1002452. [PubMed: 22241982]  [MGI Ref ID J:183297]

Colston JT; Boylston WH; Feldman MD; Jenkinson CP; de la Rosa SD; Barton A; Trevino RJ; Freeman GL; Chandrasekar B. 2007. Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload. Biochem Biophys Res Commun 354(2):552-8. [PubMed: 17250807]  [MGI Ref ID J:118183]

Denton AE; Doherty PC; Turner SJ; La Gruta NL. 2007. IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8(+) T cells. Eur J Immunol 37(2):368-75. [PubMed: 17219365]  [MGI Ref ID J:117879]

Duan RS; Zhang XM; Mix E; Quezada HC; Adem A; Zhu J. 2007. IL-18 deficiency inhibits both Th1 and Th2 cytokine production but not the clinical symptoms in experimental autoimmune neuritis. J Neuroimmunol 183(1-2):162-7. [PubMed: 17218016]  [MGI Ref ID J:124505]

Elhage R; Jawien J; Rudling M; Ljunggren HG; Takeda K; Akira S; Bayard F; Hansson GK. 2003. Reduced atherosclerosis in interleukin-18 deficient apolipoprotein E-knockout mice. Cardiovasc Res 59(1):234-40. [PubMed: 12829194]  [MGI Ref ID J:102800]

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]

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]

Gris D; Ye Z; Iocca HA; Wen H; Craven RR; Gris P; Huang M; Schneider M; Miller SD; Ting JP. 2010. NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. J Immunol 185(2):974-81. [PubMed: 20574004]  [MGI Ref ID J:162018]

Guay HM; Andreyeva TA; Garcea RL; Welsh RM; Szomolanyi-Tsuda E. 2007. MyD88 is required for the formation of long-term humoral immunity to virus infection. J Immunol 178(8):5124-31. [PubMed: 17404295]  [MGI Ref ID J:145278]

Gutcher I; Urich E; Wolter K; Prinz M; Becher B. 2006. Interleukin 18-independent engagement of interleukin 18 receptor-alpha is required for autoimmune inflammation. Nat Immunol 7(9):946-53. [PubMed: 16906165]  [MGI Ref ID J:112650]

Haddad EA; Senger LK; Takei F. 2009. An accessory role for B cells in the IL-12-induced activation of resting mouse NK cells. J Immunol 183(6):3608-15. [PubMed: 19710462]  [MGI Ref ID J:152301]

Halpern MD; Khailova L; Molla-Hosseini D; Arganbright K; Reynolds C; Yajima M; Hoshiba J; Dvorak B. 2008. Decreased development of necrotizing enterocolitis in IL-18-deficient mice. Am J Physiol Gastrointest Liver Physiol 294(1):G20-6. [PubMed: 17947451]  [MGI Ref ID J:130516]

Hanada T; Date Y; Shimbara T; Sakihara S; Murakami N; Hayashi Y; Kanai Y; Suda T; Kangawa K; Nakazato M. 2003. Central actions of neuromedin U via corticotropin-releasing hormone. Biochem Biophys Res Commun 311(4):954-8. [PubMed: 14623274]  [MGI Ref ID J:113584]

Haring JS; Harty JT. 2009. Interleukin-18-related genes are induced during the contraction phase but do not play major roles in regulating the dynamics or function of the T-cell response to Listeria monocytogenes infection. Infect Immun 77(5):1894-903. [PubMed: 19223481]  [MGI Ref ID J:148206]

Hayashi N; Yoshimoto T; Izuhara K; Matsui K; Tanaka T; Nakanishi K. 2007. T helper 1 cells stimulated with ovalbumin and IL-18 induce airway hyperresponsiveness and lung fibrosis by IFN-{gamma} and IL-13 production. Proc Natl Acad Sci U S A 104(37):14765-70. [PubMed: 17766435]  [MGI Ref ID J:124973]

He Z; Dursun B; Oh DJ; Lu L; Faubel S; Edelstein CL. 2009. Macrophages are not the source of injurious interleukin-18 in ischemic acute kidney injury in mice. Am J Physiol Renal Physiol 296(3):F535-42. [PubMed: 19129255]  [MGI Ref ID J:145703]

Hedtjarn M; Leverin AL; Eriksson K; Blomgren K; Mallard C; Hagberg H. 2002. Interleukin-18 involvement in hypoxic-ischemic brain injury. J Neurosci 22(14):5910-9. [PubMed: 12122053]  [MGI Ref ID J:124249]

Hedtjarn M; Mallard C; Arvidsson P; Hagberg H. 2005. White matter injury in the immature brain: role of interleukin-18. Neurosci Lett 373(1):16-20. [PubMed: 15555769]  [MGI Ref ID J:104826]

Hedtjarn M; Mallard C; Iwakura Y; Hagberg H. 2005. Combined deficiency of IL-1beta18, but not IL-1alphabeta, reduces susceptibility to hypoxia-ischemia in the immature brain. Dev Neurosci 27(2-4):143-8. [PubMed: 16046848]  [MGI Ref ID J:104898]

Helmby H; Grencis RK. 2002. IL-18 regulates intestinal mastocytosis and Th2 cytokine production independently of IFN-gamma during Trichinella spiralis infection. J Immunol 169(5):2553-60. [PubMed: 12193725]  [MGI Ref ID J:120688]

Henao-Mejia J; Elinav E; Jin C; Hao L; Mehal WZ; Strowig T; Thaiss CA; Kau AL; Eisenbarth SC; Jurczak MJ; Camporez JP; Shulman GI; Gordon JI; Hoffman HM; Flavell RA. 2012. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482(7384):179-85. [PubMed: 22297845]  [MGI Ref ID J:181354]

Huber S; Gagliani N; Zenewicz LA; Huber FJ; Bosurgi L; Hu B; Hedl M; Zhang W; O'Connor W Jr; Murphy AJ; Valenzuela DM; Yancopoulos GD; Booth CJ; Cho JH; Ouyang W; Abraham C; Flavell RA. 2012. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491(7423):259-63. [PubMed: 23075849]  [MGI Ref ID J:189217]

Imaeda AB; Watanabe A; Sohail MA; Mahmood S; Mohamadnejad M; Sutterwala FS; Flavell RA; Mehal WZ. 2009. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. J Clin Invest 119(2):305-14. [PubMed: 19164858]  [MGI Ref ID J:146148]

Ishii KJ; Ito S; Tamura T; Hemmi H; Conover J; Ozato K; Akira S; Klinman DM. 2005. CpG-activated Thy1.2+ dendritic cells protect against lethal Listeria monocytogenes infection. Eur J Immunol 35(8):2397-405. [PubMed: 16047338]  [MGI Ref ID J:100431]

Iwai Y; Hemmi H; Mizenina O; Kuroda S; Suda K; Steinman RM. 2008. An IFN-gamma-IL-18 signaling loop accelerates memory CD8+ T cell proliferation. PLoS ONE 3(6):e2404. [PubMed: 18545704]  [MGI Ref ID J:137144]

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Joosten LA; Koenders MI; Smeets RL; Heuvelmans-Jacobs M; Helsen MM; Takeda K; Akira S; Lubberts E; van de Loo FA; van den Berg WB. 2003. Toll-like receptor 2 pathway drives streptococcal cell wall-induced joint inflammation: critical role of myeloid differentiation factor 88. J Immunol 171(11):6145-53. [PubMed: 14634130]  [MGI Ref ID J:119063]

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Wheeler RD; Brough D; Le Feuvre RA; Takeda K; Iwakura Y; Luheshi GN; Rothwell NJ. 2003. Interleukin-18 induces expression and release of cytokines from murine glial cells: interactions with interleukin-1 beta. J Neurochem 85(6):1412-20. [PubMed: 12787061]  [MGI Ref ID J:126730]

Wieland CW; Florquin S; Pater JM; Weijer S; van der Poll T. 2006. CD4+ cells play a limited role in murine lung infection with Mycobacterium kansasii. Am J Respir Cell Mol Biol 34(2):167-73. [PubMed: 16195537]  [MGI Ref ID J:120194]

Wieland CW; Florquin S; van der Poll T. 2007. Interleukin 18 participates in the early inflammatory response and bacterial clearance during pneumonia caused by nontypeable Haemophilus influenzae. Infect Immun 75(10):5068-72. [PubMed: 17664259]  [MGI Ref ID J:125285]

Wolf G; Yirmiya R; Goshen I; Iverfeldt K; Holmlund L; Takeda K; Shavit Y. 2003. Impairment of interleukin-1 (IL-1) signaling reduces basal pain sensitivity in mice: genetic, pharmacological and developmental aspects. Pain 104(3):471-80. [PubMed: 12927619]  [MGI Ref ID J:118738]

Wyburn K; Wu H; Chen G; Yin J; Eris J; Chadban S. 2006. Interleukin-18 affects local cytokine expression but does not impact on the development of kidney allograft rejection. Am J Transplant 6(11):2612-21. [PubMed: 17049054]  [MGI Ref ID J:135970]

Yamagata S; Tomita K; Sato R; Niwa A; Higashino H; Tohda Y. 2008. Interleukin-18-deficient mice exhibit diminished chronic inflammation and airway remodelling in ovalbumin-induced asthma model. Clin Exp Immunol 154(3):295-304. [PubMed: 18826499]  [MGI Ref ID J:142814]

Zhang JH; He H; Borzychowski AM; Takeda K; Akira S; Croy BA. 2003. Analysis of cytokine regulators inducing interferon production by mouse uterine natural killer cells. Biol Reprod 69(2):404-11. [PubMed: 12646495]  [MGI Ref ID J:84561]

Zhang XM; Duan RS; Chen Z; Quezada HC; Mix E; Winblad B; Zhu J. 2007. IL-18 deficiency aggravates kainic acid-induced hippocampal neurodegeneration in C57BL/6 mice due to an overcompensation by IL-12. Exp Neurol 205(1):64-73. [PubMed: 17316614]  [MGI Ref ID J:141588]

Zhou S; Kurt-Jones EA; Cerny AM; Chan M; Bronson RT; Finberg RW. 2009. MyD88 intrinsically regulates CD4 T-cell responses. J Virol 83(4):1625-34. [PubMed: 19052080]  [MGI Ref ID J:153385]

Zorrilla EP; Sanchez-Alavez M; Sugama S; Brennan M; Fernandez R; Bartfai T; Conti B. 2007. Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency. Proc Natl Acad Sci U S A 104(26):11097-102. [PubMed: 17578927]  [MGI Ref ID J:122588]

Zwijnenburg PJ; van der Poll T; Florquin S; Akira S; Takeda K; Roord JJ; van Furth AM. 2003. Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis. J Neuroimmunol 138(1-2):31-7. [PubMed: 12742650]  [MGI Ref ID J:119043]

van de Veerdonk FL; Joosten LA; Shaw PJ; Smeekens SP; Malireddi RK; van der Meer JW; Kullberg BJ; Netea MG; Kanneganti TD. 2011. The inflammasome drives protective Th1 and Th17 cellular responses in disseminated candidiasis. Eur J Immunol 41(8):2260-8. [PubMed: 21681738]  [MGI Ref ID J:176811]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129P2 background and has been backcrossed to C57BL/6 for at least 8 generations(7/01). Coat color expected from breeding:Black
Mating System	Homozygote x Homozygote         (Female x Male)   01-MAR-06
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	000664 C57BL/6J
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.

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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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JAX^® Mice, Products & Services Conditions of Use

"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.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

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In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.