Description

Strain Information

Former Names B6.129P2-Il1rrptm1Aki    (Changed: 15-DEC-04 ) 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 N10F12N1F3 (22-JAN-09) Generation Definitions   Donating Investigator Shizuo Akira,   Research Institute for Microbial Disease

Description
Mice that are homozygous null for the Il18r1 gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Il18r1 mRNA is detected. Homozygous Il18r1 null mice are similar in phenotype to IL-18-deficient mice. They show reduced binding of IL-18 on the surface of Th1 cells, and exhibit decreased levels of interferon gamma production in response to IL-18. Natural killer cell activity is also diminished and the T helper lymphocyte response in impaired.

Development
A targeting vector containing neomycin resistance and Herpes simplex virus thymidine kinase genes was used to disrupt an exon encoding the transmembrane domain (amino acids 296-350). 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

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

Il18r1^tm1Aki/Il18r1^tm1Aki

        either: (involves: 129P2/OlaHsd) or (involves: 129P2/OlaHsd * C57BL/6)

• immune system phenotype
• abnormal T-helper 1 physiology
  • reduced production of IFN-gamma by Th1 cells in response to bacterial antigen   (MGI Ref ID J:70298)
• decreased interferon-gamma secretion
  • reduced production of IFN-gamma by Th1 cells in response to bacterial antigen   (MGI Ref ID J:70298)
• impaired natural killer cell mediated cytotoxicity
  • impaired lytic activity against pathogens   (MGI Ref ID J:70298)

View Research Applications

Research Applications

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

Il18r1^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		Il18r1tm1Aki
Allele Name		targeted mutation 1, Shizuo Akira
Allele Type		Targeted (knock-out)
Common Name(s)		Il18r1-; Il18ralpha-; Il1rrptm1Aki;
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		Il18r1, interleukin 18 receptor 1
Chromosome		1
Gene Common Name(s)		CD218a; CDw218a; IL-1Rrp; IL18RA; IL1RRP; Il18ralpha; Il1rrp; interleukin 1 receptor related protein;
Molecular Note		Replacement of the exon encoding amino acids 296-350, encoding the transmembrane region, with a neomycin cassette. No mRNA was detected in liver from homozygous mutant animals, as assayed by RT-PCR. [MGI Ref ID J:70298]

Genotyping

Genotyping Information

Genotyping Protocols

Il18rl^tm1aki, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Hoshino K; Tsutsui H; Kawai T; Takeda K; Nakanishi K; Takeda Y; Akira S. 1999. Cutting edge: generation of IL-18 receptor-deficient mice: evidence for IL-1 receptor-related protein as an essential IL-18 binding receptor. J Immunol 162(9):5041-4. [PubMed: 10227969]  [MGI Ref ID J:70298]

Additional References

Il18r1^tm1Aki related

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]

Babcock AA; Toft-Hansen H; Owens T. 2008. Signaling through MyD88 regulates leukocyte recruitment after brain injury. J Immunol 181(9):6481-90. [PubMed: 18941239]  [MGI Ref ID J:140719]

Chen CJ; Kono H; Golenbock D; Reed G; Akira S; Rock KL. 2007. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat Med 13(7):851-6. [PubMed: 17572686]  [MGI Ref ID J:125088]

Chen CJ; Shi Y; Hearn A; Fitzgerald K; Golenbock D; Reed G; Akira S; Rock KL. 2006. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest 116(8):2262-71. [PubMed: 16886064]  [MGI Ref ID J:113110]

Conforti-Andreoni C; Spreafico R; Qian HL; Riteau N; Ryffel B; Ricciardi-Castagnoli P; Mortellaro A. 2011. Uric acid-driven Th17 differentiation requires inflammasome-derived IL-1 and IL-18. J Immunol 187(11):5842-50. [PubMed: 22058415]  [MGI Ref ID J:179683]

Coulouarn C; Corlu A; Glaise D; Guenon I; Thorgeirsson SS; Clement B. 2012. Hepatocyte-stellate cell cross-talk in the liver engenders a permissive inflammatory microenvironment that drives progression in hepatocellular carcinoma. Cancer Res 72(10):2533-42. [PubMed: 22419664]  [MGI Ref ID J:189352]

Ellebedy AH; Lupfer C; Ghoneim HE; Debeauchamp J; Kanneganti TD; Webby RJ. 2011. Inflammasome-independent role of the apoptosis-associated speck-like protein containing CARD (ASC) in the adjuvant effect of MF59. Proc Natl Acad Sci U S A 108(7):2927-32. [PubMed: 21270336]  [MGI Ref ID J:169092]

Fremond CM; Togbe D; Doz E; Rose S; Vasseur V; Maillet I; Jacobs M; Ryffel B; Quesniaux VF. 2007. IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection. J Immunol 179(2):1178-89. [PubMed: 17617611]  [MGI Ref ID J:149392]

Gasse P; Mary C; Guenon I; Noulin N; Charron S; Schnyder-Candrian S; Schnyder B; Akira S; Quesniaux VF; Lagente V; Ryffel B; Couillin I. 2007. IL-1R1/MyD88 signaling and the inflammasome are essential in pulmonary inflammation and fibrosis in mice. J Clin Invest 117(12):3786-99. [PubMed: 17992263]  [MGI Ref ID J:130776]

Gasse P; Riteau N; Charron S; Girre S; Fick L; Petrilli V; Tschopp J; Lagente V; Quesniaux VF; Ryffel B; Couillin I. 2009. Uric acid is a danger signal activating NALP3 inflammasome in lung injury inflammation and fibrosis. Am J Respir Crit Care Med 179(10):903-13. [PubMed: 19218193]  [MGI Ref ID J:164986]

Grivennikov SI; Wang K; Mucida D; Stewart CA; Schnabl B; Jauch D; Taniguchi K; Yu GY; Osterreicher CH; Hung KE; Datz C; Feng Y; Fearon ER; Oukka M; Tessarollo L; Coppola V; Yarovinsky F; Cheroutre H; Eckmann L; Trinchieri G; Karin M. 2012. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491(7423):254-8. [PubMed: 23034650]  [MGI Ref ID J:189226]

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]

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]

Hwang I; Scott JM; Kakarla T; Duriancik DM; Choi S; Cho C; Lee T; Park H; French AR; Beli E; Gardner E; Kim S. 2012. Activation mechanisms of natural killer cells during influenza virus infection. PLoS One 7(12):e51858. [PubMed: 23300570]  [MGI Ref ID J:195732]

Ingram JT; Yi JS; Zajac AJ. 2011. Exhausted CD8 T cells downregulate the IL-18 receptor and become unresponsive to inflammatory cytokines and bacterial co-infections. PLoS Pathog 7(9):e1002273. [PubMed: 21980291]  [MGI Ref ID J:183336]

Kang MJ; Homer RJ; Gallo A; Lee CG; Crothers KA; Cho SJ; Rochester C; Cain H; Chupp G; Yoon HJ; Elias JA. 2007. IL-18 is induced and IL-18 receptor alpha plays a critical role in the pathogenesis of cigarette smoke-induced pulmonary emphysema and inflammation. J Immunol 178(3):1948-59. [PubMed: 17237446]  [MGI Ref ID J:143631]

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]

Klekotka PA; Yang L; Yokoyama WM. 2010. Contrasting roles of the IL-1 and IL-18 receptors in MyD88-dependent contact hypersensitivity. J Invest Dermatol 130(1):184-91. [PubMed: 19657352]  [MGI Ref ID J:159581]

Lewis EC; Dinarello CA. 2006. Responses of IL-18- and IL-18 receptor-deficient pancreatic islets with convergence of positive and negative signals for the IL-18 receptor. Proc Natl Acad Sci U S A 103(45):16852-7. [PubMed: 17075045]  [MGI Ref ID J:117139]

Maxwell JR; Yadav R; Rossi RJ; Ruby CE; Weinberg AD; Aguila HL; Vella AT. 2006. IL-18 bridges innate and adaptive immunity through IFN-gamma and the CD134 pathway. J Immunol 177(1):234-45. [PubMed: 16785519]  [MGI Ref ID J:134442]

Miura K; Matsuo J; Rahman MA; Kumagai Y; Li X; Rikihisa Y. 2011. Ehrlichia chaffeensis Induces Monocyte Inflammatory Responses through MyD88, ERK, and NF-kappaB but Not through TRIF, Interleukin-1 Receptor 1 (IL-1R1)/IL-18R1, or Toll-Like Receptors. Infect Immun 79(12):4947-56. [PubMed: 21930764]  [MGI Ref ID J:178488]

Netea MG; Joosten LA; Lewis E; Jensen DR; Voshol PJ; Kullberg BJ; Tack CJ; van Krieken H; Kim SH; Stalenhoef AF; van de Loo FA; Verschueren I; Pulawa L; Akira S; Eckel RH; Dinarello CA; van den Berg W; van der Meer JW. 2006. Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance. Nat Med 12(6):650-656. [PubMed: 16732281]  [MGI Ref ID J:109552]

Okamoto M; Kato S; Oizumi K; Kinoshita M; Inoue Y; Hoshino K; Akira S; McKenzie AN; Young HA; Hoshino T. 2002. Interleukin 18 (IL-18) in synergy with IL-2 induces lethal lung injury in mice: a potential role for cytokines, chemokines, and natural killer cells in the pathogenesis of interstitial pneumonia. Blood 99(4):1289-98. [PubMed: 11830478]  [MGI Ref ID J:74714]

Rahman AH; Cui W; Larosa DF; Taylor DK; Zhang J; Goldstein DR; Wherry EJ; Kaech SM; Turka LA. 2008. MyD88 plays a critical T cell-intrinsic role in supporting CD8 T cell expansion during acute lymphocytic choriomeningitis virus infection. J Immunol 181(6):3804-10. [PubMed: 18768833]  [MGI Ref ID J:139113]

Scheibner KA; Lutz MA; Boodoo S; Fenton MJ; Powell JD; Horton MR. 2006. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J Immunol 177(2):1272-81. [PubMed: 16818787]  [MGI Ref ID J:135038]

Schneider BE; Korbel D; Hagens K; Koch M; Raupach B; Enders J; Kaufmann SH; Mittrucker HW; Schaible UE. 2010. A role for IL-18 in protective immunity against Mycobacterium tuberculosis. Eur J Immunol 40(2):396-405. [PubMed: 19950174]  [MGI Ref ID J:157785]

Seki E; Tsutsui H; Tsuji NM; Hayashi N; Adachi K; Nakano H; Futatsugi-Yumikura S; Takeuchi O; Hoshino K; Akira S; Fujimoto J; Nakanishi K. 2002. Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice. J Immunol 169(7):3863-8. [PubMed: 12244183]  [MGI Ref ID J:120385]

Shannon P; Sabha N; Lau N; Kamnasaran D; Gutmann DH; Guha A. 2005. Pathological and Molecular Progression of Astrocytomas in a GFAP:12V-Ha-Ras Mouse Astrocytoma Model. Am J Pathol 167(3):859-67. [PubMed: 16127163]  [MGI Ref ID J:100679]

Sheahan T; Morrison TE; Funkhouser W; Uematsu S; Akira S; Baric RS; Heise MT. 2008. MyD88 is required for protection from lethal infection with a mouse-adapted SARS-CoV. PLoS Pathog 4(12):e1000240. [PubMed: 19079579]  [MGI Ref ID J:162707]

Srinivasan A; Salazar-Gonzalez RM; Jarcho M; Sandau MM; Lefrancois L; McSorley SJ. 2007. Innate immune activation of CD4 T cells in salmonella-infected mice is dependent on IL-18. J Immunol 178(10):6342-9. [PubMed: 17475863]  [MGI Ref ID J:146116]

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]

Terme M; Ullrich E; Aymeric L; Meinhardt K; Desbois M; Delahaye N; Viaud S; Ryffel B; Yagita H; Kaplanski G; Prevost-Blondel A; Kato M; Schultze JL; Tartour E; Kroemer G; Chaput N; Zitvogel L. 2011. IL-18 Induces PD-1-Dependent Immunosuppression in Cancer. Cancer Res 71(16):5393-5399. [PubMed: 21724589]  [MGI Ref ID J:175445]

Togbe D; Aurore G; Noulin N; Quesniaux VF; Schnyder-Candrian S; Schnyder B; Vasseur V; Akira S; Hoebe K; Beutler B; Ryffel B; Couillin I. 2006. Nonredundant roles of TIRAP and MyD88 in airway response to endotoxin, independent of TRIF, IL-1 and IL-18 pathways. Lab Invest 86(11):1126-35. [PubMed: 16983331]  [MGI Ref ID J:114842]

Vladimer GI; Weng D; Paquette SW; Vanaja SK; Rathinam VA; Aune MH; Conlon JE; Burbage JJ; Proulx MK; Liu Q; Reed G; Mecsas JC; Iwakura Y; Bertin J; Goguen JD; Fitzgerald KA; Lien E. 2012. The NLRP12 inflammasome recognizes Yersinia pestis. Immunity 37(1):96-107. [PubMed: 22840842]  [MGI Ref ID J:187388]

Wan Y; Kim TW; Yu M; Zhou H; Yamashita M; Kang Z; Yin W; Wang JA; Thomas J; Sen GC; Stark GR; Li X. 2011. The Dual Functions of IL-1 Receptor-Associated Kinase 2 in TLR9-Mediated IFN and Proinflammatory Cytokine Production. J Immunol 186(5):3006-14. [PubMed: 21270393]  [MGI Ref ID J:169397]

Wang JP; Lee CK; Akalin A; Finberg RW; Levitz SM. 2011. Contributions of the MyD88-Dependent Receptors IL-18R, IL-1R, and TLR9 to Host Defenses following Pulmonary Challenge with Cryptococcus neoformans. PLoS One 6(10):e26232. [PubMed: 22039448]  [MGI Ref ID J:178086]

Wuthrich M; Gern B; Hung CY; Ersland K; Rocco N; Pick-Jacobs J; Galles K; Filutowicz H; Warner T; Evans M; Cole G; Klein B. 2011. Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. J Clin Invest 121(2):554-68. [PubMed: 21206087]  [MGI Ref ID J:171835]

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 6 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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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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