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)   23-AUG-06 Species laboratory mouse Generation N7+F13 (14-MAR-11) Generation Definitions   Donating Investigator Dr. Richard A. Flavell,   Yale University School of Medicine

Description
Homozygous mice are viable and fertile with normal lymphoid and myeloid cellularity and no intestinal inflammation up to 6 months of age. Homozygotes do not express the targeted gene in spleen or intestinal crypts. Null mice, as well as antigen presenting cells derived from them, lack the protective immunity (IgG1, interleukin-6, and NF-kappaB-related responses) normally afforded by endogenous protein recognition of its ligand, bacterial muramyl dipeptide (MDP). Mice homozygous for the mutation have increased susceptibility to oral (intragastric) bacterial challenge and diminished cryptdins. This mouse may be useful in studies of Crohn's disease and other inflammatory bowel diseases, innate immunity, signal transduction, and bacterial susceptibility.

Development
A targeting vector was designed to replace exon 3 of the endogenous gene (containing the second caspase recruitment domain (CARD) and nucleotide-binding oligomerization domain (NOD)) with a lox-P-flanked neomycin resistance gene. The construct was electroporated into 129S1/Sv-derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6 females. The donating investigator reported that the resulting heterozygotes were backcrossed to C57BL/6 mice (see SNP note below) for 6 generations before arrival at The Jackson Laboratory. Upon arrival, heterozygous males were bred to C57BL/6J for one generation and then maintained by crossing mutant mice.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 1 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Blau Syndrome   (NOD2) Inflammatory Bowel Disease 1; IBD1   (NOD2) Psoriatic Arthritis, Susceptibility to Psoriatic Arthritis, Susceptibility to, 1; PSORAS1   (NOD2) Sarcoidosis, Early-Onset   (NOD2)

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.

Nod2^tm1Flv/Nod2^tm1Flv

        involves: 129S1/Sv * C57BL/6

• immune system phenotype
• abnormal macrophage physiology
  • the synergistic effect of bacterial muramyl dipeptide and TLR ligands on the production of IL6 and IL12 is absent in mutant macrophages   (MGI Ref ID J:96035)
  • bone marrow derived macrophages produce less IL-6 and TNF when cultured in the presence of L. monocytogenes   (MGI Ref ID J:132126)
  • in macrophages pre-treated with TLR ligands (i.e. "tolerized"), macrophages produce significantly less inflammatory cytokines upon incubation with L. monocytogenes than controls that were LPS pre-treated   (MGI Ref ID J:132126)
• altered susceptibility to infection
  • homozygotes are more susceptible to Listeria monocytogenes infection via intragastric exposure but not via intraperitoneal or intravenous exposure   (MGI Ref ID J:96035)
  • however, no signs of intestinal inflammation and no difference in susceptibility to dextran sulfate induced colitis are seen   (MGI Ref ID J:96035)
• decreased IgG level
  • decreased antigen specific Ig and IgG1 production are seen following stimulation with bacterial muramyl dipeptide and HSA; however, production is normal when stimulated by HAS plus an artificial TLR7 ligand   (MGI Ref ID J:96035)
• decreased interleukin-6 secretion
  • bone marrow derived macrophages secrete 73% the amount of IL-6 as wild-type controls due in response to culturing with L. monocytogenes   (MGI Ref ID J:132126)
  • a similar relative reduction is observed when macrophages are pre-treated with LPS prior to L. monocytogenes incubation   (MGI Ref ID J:132126)
• decreased susceptibility to endotoxin shock
  • homozygotes are resistant to endotoxin shock produced by LPS following bacterial muramyl dipeptide priming but not to endotoxin shock produced by LPS alone   (MGI Ref ID J:96035)
• decreased tumor necrosis factor secretion
  • bone marrow derived macrophages secrete 77% the amount of TNF as wild-type controls in response to culturing with L. monocytogenes   (MGI Ref ID J:132126)
  • TNF secretion is 57% that of controls when macrophages are pre-treated with LPS prior to L. monocytogenes incubation   (MGI Ref ID J:132126)

Nod2^tm1Flv/Nod2^tm1Flv

        involves: 129S1/Sv

• mortality/aging
• increased susceptibility to bacterial infection induced morbidity/mortality
  • when infected with Sanger 476, a methicillin-susceptible S. aureus strain, or MW2, a methicillin-resistant S. aureus strain   (MGI Ref ID J:147177)
• immune system phenotype
• abnormal T-helper 1 physiology
  • increase in the levels of Th1 derived cytokines   (MGI Ref ID J:147177)
• abnormal response to infection
  • bacterial loads are significantly higher at 18 hours in the kidney, peritoneal fluid, blood and mesenteric lymph nodes after bacterial infection   (MGI Ref ID J:147177)
• • increased susceptibility to bacterial infection induced morbidity/mortality
    • when infected with Sanger 476, a methicillin-susceptible S. aureus strain, or MW2, a methicillin-resistant S. aureus strain   (MGI Ref ID J:147177)
• impaired macrophage phagocytosis
  • the phagocytic index is significantly lower in macrophage   (MGI Ref ID J:147177)
• impaired neutrophil phagocytosis
  • in an in vitro assay the neutrophils from wild-type control mice have a higher number of internalized S. aureus   (MGI Ref ID J:147177)
• increased circulating interferon-gamma level
  • after S. aureus infection   (MGI Ref ID J:147177)
• increased circulating interleukin-2 level
  • after S. aureus infection   (MGI Ref ID J:147177)
• increased circulating tumor necrosis factor level
  • after S. aureus infection   (MGI Ref ID J:147177)
• increased leukocyte cell number
  • in the blood of mice at 6, 12, and 18 hours post infection with S.aureus   (MGI Ref ID J:147177)
• • increased neutrophil cell number
    • in the peritoneal fluid at 12 and 18 hours post infection with S.aureus   (MGI Ref ID J:147177)
• hematopoietic system phenotype
• increased leukocyte cell number
  • in the blood of mice at 6, 12, and 18 hours post infection with S.aureus   (MGI Ref ID J:147177)
• • increased neutrophil cell number
    • in the peritoneal fluid at 12 and 18 hours post infection with S.aureus   (MGI Ref ID J:147177)
• homeostasis/metabolism phenotype
• increased circulating interferon-gamma level
  • after S. aureus infection   (MGI Ref ID J:147177)
• increased circulating interleukin-2 level
  • after S. aureus infection   (MGI Ref ID J:147177)
• increased circulating tumor necrosis factor level
  • after S. aureus infection   (MGI Ref ID J:147177)

Nod2^tm1Flv/Nod2^tm1Flv

        C.129S1-Nod2^tm1Flv

• immune system phenotype
• decreased susceptibility to induced arthritis
  • in response to peptidoglycan or muramyl dipeptide (MDP), mice fail to develop arthritis unlike similarly treated wild-type mice   (MGI Ref ID J:178054)
• skeleton phenotype
• decreased susceptibility to induced arthritis
  • in response to peptidoglycan or muramyl dipeptide (MDP), mice fail to develop arthritis unlike similarly treated wild-type mice   (MGI Ref ID J:178054)

View Research Applications

Research Applications

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

Cell Biology Research
Signal Transduction

Hematological Research
Immunological Defects

Immunology, Inflammation and Autoimmunity Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers
      genes regulating susceptibility to infectious disease and endotoxin
Immunodeficiency
      Inflammatory bowel disease
      Tlr deficiency
      defects in humoral immune responses
Inflammation
      Inflammatory bowel disease
      Tlr deficiency
Intracellular Signaling Molecules

Research Tools
Genetics Research
      Mutagenesis and Transgenesis
      Mutagenesis and Transgenesis: transcriptional activation
Immunology and Inflammation Research
      Macrophage Deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Nod2tm1Flv
Allele Name		targeted mutation 1, Richard A Flavell
Allele Type		Targeted (knock-out)
Common Name(s)		Nod2-;
Mutation Made By		Dr. Richard Flavell,   Yale University School of Medicine
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		W9.5/W95
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Nod2, nucleotide-binding oligomerization domain containing 2
Chromosome		8
Gene Common Name(s)		ACUG; BLAU; CARD15; CD; CLR16.3; Card15; F830032C23Rik; IBD1; NLRC2; NOD2B; PSORAS1; RIKEN cDNA F830032C23 gene; caspase recruitment domain family, member 15;
Molecular Note		A loxP-flanked neo replaced exon 3, encoding the CARD domain and P-loop of the NOD domain. Spleens of mutant animals demonstrated a lack of protein by immunoblot analysis. [MGI Ref ID J:96035]

Genotyping

Genotyping Information

Genotyping Protocols

Nod2^tm1Flv, Standard PCR
Nod2^tm1Flv, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kobayashi KS; Chamaillard M; Ogura Y; Henegariu O; Inohara N; Nunez G; Flavell RA. 2005. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307(5710):731-4. [PubMed: 15692051]  [MGI Ref ID J:96035]

Additional References

Nod2^tm1Flv related

Abdalla H; Srinivasan L; Shah S; Mayer-Barber KD; Sher A; Sutterwala FS; Briken V. 2012. Mycobacterium tuberculosis infection of dendritic cells leads to partially caspase-1/11-independent IL-1beta and IL-18 secretion but not to pyroptosis. PLoS One 7(7):e40722. [PubMed: 22911706]  [MGI Ref ID J:189888]

Ali SR; Timmer AM; Bilgrami S; Park EJ; Eckmann L; Nizet V; Karin M. 2011. Anthrax Toxin Induces Macrophage Death by p38 MAPK Inhibition but Leads to Inflammasome Activation via ATP Leakage. Immunity 35(1):34-44. [PubMed: 21683629]  [MGI Ref ID J:174307]

Anand PK; Tait SW; Lamkanfi M; Amer AO; Nunez G; Pages G; Pouyssegur J; McGargill MA; Green DR; Kanneganti TD. 2011. TLR2 and RIP2 Pathways Mediate Autophagy of Listeria monocytogenes via Extracellular Signal-regulated Kinase (ERK) Activation. J Biol Chem 286(50):42981-91. [PubMed: 22033934]  [MGI Ref ID J:178691]

Berrington WR; Iyer R; Wells RD; Smith KD; Skerrett SJ; Hawn TR. 2010. NOD1 and NOD2 regulation of pulmonary innate immunity to Legionella pneumophila. Eur J Immunol 40(12):3519-27. [PubMed: 21108472]  [MGI Ref ID J:174576]

Biswas A; Liu YJ; Hao L; Mizoguchi A; Salzman NH; Bevins CL; Kobayashi KS. 2010. Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum. Proc Natl Acad Sci U S A 107(33):14739-44. [PubMed: 20679225]  [MGI Ref ID J:163705]

Caetano BC; Biswas A; Lima DS Jr; Benevides L; Mineo TW; Horta CV; Lee KH; Silva JS; Gazzinelli RT; Zamboni DS; Kobayashi KS. 2011. Intrinsic expression of Nod2 in CD4+ T lymphocytes is not necessary for the development of cell-mediated immunity and host resistance to Toxoplasma gondii. Eur J Immunol 41(12):3627-31. [PubMed: 22002196]  [MGI Ref ID J:179620]

Carow B; Ye X; Gavier-Widen D; Bhuju S; Oehlmann W; Singh M; Skold M; Ignatowicz L; Yoshimura A; Wigzell H; Rottenberg ME. 2011. Silencing suppressor of cytokine signaling-1 (SOCS1) in macrophages improves Mycobacterium tuberculosis control in an interferon-gamma (IFN-gamma)-dependent manner. J Biol Chem 286(30):26873-87. [PubMed: 21622562]  [MGI Ref ID J:175389]

Chauhan VS; Sterka DG Jr; Furr SR; Young AB; Marriott I. 2009. NOD2 plays an important role in the inflammatory responses of microglia and astrocytes to bacterial CNS pathogens. Glia 57(4):414-23. [PubMed: 18803303]  [MGI Ref ID J:156220]

Chen L; Chen Z; Baker K; Halvorsen EM; da Cunha AP; Flak MB; Gerber G; Huang YH; Hosomi S; Arthur JC; Dery KJ; Nagaishi T; Beauchemin N; Holmes KV; Ho JW; Shively JE; Jobin C; Onderdonk AB; Bry L; Weiner HL; Higgins DE; Blumberg RS. 2012. The short isoform of the CEACAM1 receptor in intestinal T cells regulates mucosal immunity and homeostasis via Tfh cell induction. Immunity 37(5):930-46. [PubMed: 23123061]  [MGI Ref ID J:190980]

Cho JS; Guo Y; Ramos RI; Hebroni F; Plaisier SB; Xuan C; Granick JL; Matsushima H; Takashima A; Iwakura Y; Cheung AL; Cheng G; Lee DJ; Simon SI; Miller LS. 2012. Neutrophil-derived IL-1beta is sufficient for abscess formation in immunity against Staphylococcus aureus in mice. PLoS Pathog 8(11):e1003047. [PubMed: 23209417]  [MGI Ref ID J:195003]

Chung SW; Liu X; Macias AA; Baron RM; Perrella MA. 2008. Heme oxygenase-1-derived carbon monoxide enhances the host defense response to microbial sepsis in mice. J Clin Invest 118(1):239-47. [PubMed: 18060048]  [MGI Ref ID J:130827]

Clarke TB; Davis KM; Lysenko ES; Zhou AY; Yu Y; Weiser JN. 2010. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat Med 16(2):228-31. [PubMed: 20081863]  [MGI Ref ID J:157078]

Craven M; Egan CE; Dowd SE; McDonough SP; Dogan B; Denkers EY; Bowman D; Scherl EJ; Simpson KW. 2012. Inflammation drives dysbiosis and bacterial invasion in murine models of ileal Crohn's disease. PLoS One 7(7):e41594. [PubMed: 22848538]  [MGI Ref ID J:189701]

Damgaard RB; Nachbur U; Yabal M; Wong WW; Fiil BK; Kastirr M; Rieser E; Rickard JA; Bankovacki A; Peschel C; Ruland J; Bekker-Jensen S; Mailand N; Kaufmann T; Strasser A; Walczak H; Silke J; Jost PJ; Gyrd-Hansen M. 2012. The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity. Mol Cell 46(6):746-58. [PubMed: 22607974]  [MGI Ref ID J:188020]

Datta SK; Sabet M; Nguyen KP; Valdez PA; Gonzalez-Navajas JM; Islam S; Mihajlov I; Fierer J; Insel PA; Webster NJ; Guiney DG; Raz E. 2010. Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax. Proc Natl Acad Sci U S A 107(23):10638-43. [PubMed: 20479237]  [MGI Ref ID J:165056]

Davis KM; Nakamura S; Weiser JN. 2011. Nod2 sensing of lysozyme-digested peptidoglycan promotes macrophage recruitment and clearance of S. pneumoniae colonization in mice. J Clin Invest 121(9):3666-76. [PubMed: 21841315]  [MGI Ref ID J:178245]

Deshmukh HS; Hamburger JB; Ahn SH; McCafferty DG; Yang SR; Fowler VG Jr. 2009. Critical role of NOD2 in regulating the immune response to Staphylococcus aureus. Infect Immun 77(4):1376-82. [PubMed: 19139201]  [MGI Ref ID J:147177]

Dickinson GS; Piccone H; Sun G; Lien E; Gatto L; Alugupalli KR. 2010. Toll-like receptor 2 deficiency results in impaired antibody responses and septic shock during Borrelia hermsii infection. Infect Immun 78(11):4579-88. [PubMed: 20696824]  [MGI Ref ID J:165032]

Divangahi M; Mostowy S; Coulombe F; Kozak R; Guillot L; Veyrier F; Kobayashi KS; Flavell RA; Gros P; Behr MA. 2008. NOD2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity. J Immunol 181(10):7157-65. [PubMed: 18981137]  [MGI Ref ID J:140937]

Hasegawa M; Yamazaki T; Kamada N; Tawaratsumida K; Kim YG; Nunez G; Inohara N. 2011. Nucleotide-binding oligomerization domain 1 mediates recognition of Clostridium difficile and induces neutrophil recruitment and protection against the pathogen. J Immunol 186(8):4872-80. [PubMed: 21411735]  [MGI Ref ID J:172515]

Hsu LC; Ali SR; McGillivray S; Tseng PH; Mariathasan S; Humke EW; Eckmann L; Powell JJ; Nizet V; Dixit VM; Karin M. 2008. A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci U S A 105(22):7803-8. [PubMed: 18511561]  [MGI Ref ID J:169881]

Ippagunta SK; Malireddi RK; Shaw PJ; Neale GA; Walle LV; Fukui Y; Green DR; Lamkanfi M; Kanneganti TD. 2012. Addendum: defective Dock2 expression in a subset of ASC-deficient mouse lines. Nat Immunol 13(7):701-2. [PubMed: 22905357]  [MGI Ref ID J:187712]

Iyer JK; Khurana T; Langer M; West CM; Ballard JD; Metcalf JP; Merkel TJ; Coggeshall KM. 2010. Inflammatory Cytokine Response to Bacillus anthracis Peptidoglycan Requires Phagocytosis and Lysosomal Trafficking. Infect Immun 78(6):2418-28. [PubMed: 20308305]  [MGI Ref ID J:159862]

Jamontt J; Petit S; Clark N; Parkinson SJ; Smith P. 2013. Nucleotide-Binding Oligomerization Domain 2 Signaling Promotes Hyperresponsive Macrophages and Colitis in IL-10-Deficient Mice. J Immunol 190(6):2948-58. [PubMed: 23396949]  [MGI Ref ID J:193595]

Kanneganti TD; Lamkanfi M; Kim YG; Chen G; Park JH; Franchi L; Vandenabeele P; Nunez G. 2007. Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling. Immunity 26(4):433-43. [PubMed: 17433728]  [MGI Ref ID J:123579]

Kayagaki N; Warming S; Lamkanfi M; Vande Walle L; Louie S; Dong J; Newton K; Qu Y; Liu J; Heldens S; Zhang J; Lee WP; Roose-Girma M; Dixit VM. 2011. Non-canonical inflammasome activation targets caspase-11. Nature 479(7371):117-21. [PubMed: 22002608]  [MGI Ref ID J:193522]

Kim YG; Kamada N; Shaw MH; Warner N; Chen GY; Franchi L; Nunez G. 2011. The Nod2 Sensor Promotes Intestinal Pathogen Eradication via the Chemokine CCL2-Dependent Recruitment of Inflammatory Monocytes. Immunity 34(5):769-80. [PubMed: 21565531]  [MGI Ref ID J:172121]

Kim YG; Park JH; Shaw MH; Franchi L; Inohara N; Nunez G. 2008. The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands. Immunity 28(2):246-57. [PubMed: 18261938]  [MGI Ref ID J:132126]

Kim YG; Shaw MH; Warner N; Park JH; Chen F; Ogura Y; Nunez G. 2011. Cutting edge: Crohn's disease-associated Nod2 mutation limits production of proinflammatory cytokines to protect the host from Enterococcus faecalis-induced lethality. J Immunol 187(6):2849-52. [PubMed: 21849681]  [MGI Ref ID J:179232]

Koppe U; Hogner K; Doehn JM; Muller HC; Witzenrath M; Gutbier B; Bauer S; Pribyl T; Hammerschmidt S; Lohmeyer J; Suttorp N; Herold S; Opitz B. 2012. Streptococcus pneumoniae stimulates a STING- and IFN regulatory factor 3-dependent type I IFN production in macrophages, which regulates RANTES production in macrophages, cocultured alveolar epithelial cells, and mouse lungs. J Immunol 188(2):811-7. [PubMed: 22156592]  [MGI Ref ID J:180799]

Lacroix-Lamande S; Fanton d'Andon M; Michel E; Ratet G; Philpott DJ; Girardin SE; Boneca IG; Vandewalle A; Werts C. 2012. Downregulation of the Na/K-ATPase Pump by Leptospiral Glycolipoprotein Activates the NLRP3 Inflammasome. J Immunol 188(6):2805-14. [PubMed: 22323544]  [MGI Ref ID J:181854]

Liu X; Chauhan VS; Marriott I. 2010. NOD2 contributes to the inflammatory responses of primary murine microglia and astrocytes to Staphylococcus aureus. Neurosci Lett 474(2):93-8. [PubMed: 20226841]  [MGI Ref ID J:159903]

Liu X; Chauhan VS; Young AB; Marriott I. 2010. NOD2 mediates inflammatory responses of primary murine glia to Streptococcus pneumoniae. Glia 58(7):839-47. [PubMed: 20091781]  [MGI Ref ID J:167893]

Loving CL; Osorio M; Kim YG; Nunez G; Hughes MA; Merkel TJ. 2009. Nod1/Nod2-mediated recognition plays a critical role in induction of adaptive immunity to anthrax after aerosol exposure. Infect Immun 77(10):4529-37. [PubMed: 19620350]  [MGI Ref ID J:153262]

Marina-Garcia N; Franchi L; Kim YG; Miller D; McDonald C; Boons GJ; Nunez G. 2008. Pannexin-1-Mediated Intracellular Delivery of Muramyl Dipeptide Induces Caspase-1 Activation via Cryopyrin/NLRP3 Independently of Nod2. J Immunol 180(6):4050-7. [PubMed: 18322214]  [MGI Ref ID J:132931]

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]

Miller JC; Maylor-Hagen H; Ma Y; Weis JH; Weis JJ. 2010. The Lyme disease spirochete Borrelia burgdorferi utilizes multiple ligands, including RNA, for interferon regulatory factor 3-dependent induction of type I interferon-responsive genes. Infect Immun 78(7):3144-53. [PubMed: 20404081]  [MGI Ref ID J:160987]

Muller P; Muller-Anstett M; Wagener J; Gao Q; Kaesler S; Schaller M; Biedermann T; Gotz F. 2010. The Staphylococcus aureus Lipoprotein SitC Colocalizes with Toll-Like Receptor 2 (TLR2) in Murine Keratinocytes and Elicits Intracellular TLR2 Accumulation. Infect Immun 78(10):4243-50. [PubMed: 20679445]  [MGI Ref ID J:164240]

Nakamura S; Davis KM; Weiser JN. 2011. Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice. J Clin Invest 121(9):3657-65. [PubMed: 21841308]  [MGI Ref ID J:178251]

Pan Q; Mathison J; Fearns C; Kravchenko VV; Da Silva Correia J; Hoffman HM; Kobayashi KS; Bertin J; Grant EP; Coyle AJ; Sutterwala FS; Ogura Y; Flavell RA; Ulevitch RJ. 2007. MDP-induced interleukin-1{beta} processing requires Nod2 and CIAS1/NALP3. J Leukoc Biol 82(1):177-83. [PubMed: 17403772]  [MGI Ref ID J:122657]

Park JH; Kim YG; McDonald C; Kanneganti TD; Hasegawa M; Body-Malapel M; Inohara N; Nunez G. 2007. RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. J Immunol 178(4):2380-6. [PubMed: 17277144]  [MGI Ref ID J:143980]

Penack O; Smith OM; Cunningham-Bussel A; Liu X; Rao U; Yim N; Na IK; Holland AM; Ghosh A; Lu SX; Jenq RR; Liu C; Murphy GF; Brandl K; van den Brink MR. 2009. NOD2 regulates hematopoietic cell function during graft-versus-host disease. J Exp Med 206(10):2101-10. [PubMed: 19737867]  [MGI Ref ID J:153357]

Petnicki-Ocwieja T; Hrncir T; Liu YJ; Biswas A; Hudcovic T; Tlaskalova-Hogenova H; Kobayashi KS. 2009. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc Natl Acad Sci U S A 106(37):15813-8. [PubMed: 19805227]  [MGI Ref ID J:153244]

Poole JA; Kielian T; Wyatt TA; Gleason AM; Stone J; Palm K; West WW; Romberger DJ. 2011. Organic dust augments nucleotide-binding oligomerization domain expression via an NF-{kappa}B pathway to negatively regulate inflammatory responses. Am J Physiol Lung Cell Mol Physiol 301(3):L296-306. [PubMed: 21665963]  [MGI Ref ID J:176330]

Rosenzweig HL; Galster K; Vance EE; Ensign-Lewis J; Nunez G; Davey MP; Rosenbaum JT. 2011. NOD2 deficiency results in increased susceptibility to peptidoglycan-induced uveitis in mice. Invest Ophthalmol Vis Sci 52(7):4106-12. [PubMed: 21296813]  [MGI Ref ID J:181443]

Rosenzweig HL; Jann MM; Glant TT; Martin TM; Planck SR; van Eden W; van Kooten PJ; Flavell RA; Kobayashi KS; Rosenbaum JT; Davey MP. 2009. Activation of nucleotide oligomerization domain 2 exacerbates a murine model of proteoglycan-induced arthritis. J Leukoc Biol 85(4):711-8. [PubMed: 19129483]  [MGI Ref ID J:146911]

Rosenzweig HL; Kawaguchi T; Martin TM; Planck SR; Davey MP; Rosenbaum JT. 2009. Nucleotide oligomerization domain-2 (NOD2)-induced uveitis: dependence on IFN-gamma. Invest Ophthalmol Vis Sci 50(4):1739-45. [PubMed: 19098321]  [MGI Ref ID J:146921]

Rosenzweig HL; Martin TM; Jann MM; Planck SR; Davey MP; Kobayashi K; Flavell RA; Rosenbaum JT. 2008. NOD2, the gene responsible for familial granulomatous uveitis, in a mouse model of uveitis. Invest Ophthalmol Vis Sci 49(4):1518-24. [PubMed: 18385071]  [MGI Ref ID J:136140]

Rosenzweig HL; Martin TM; Planck SR; Galster K; Jann MM; Davey MP; Kobayashi K; Flavell RA; Rosenbaum JT. 2008. Activation of NOD2 in vivo induces IL-1beta production in the eye via caspase-1 but results in ocular inflammation independently of IL-1 signaling. J Leukoc Biol 84(2):529-36. [PubMed: 18495787]  [MGI Ref ID J:138433]

Sabbah A; Chang TH; Harnack R; Frohlich V; Tominaga K; Dube PH; Xiang Y; Bose S. 2009. Activation of innate immune antiviral responses by Nod2. Nat Immunol 10(10):1073-80. [PubMed: 19701189]  [MGI Ref ID J:152795]

Saha S; Qi J; Wang S; Wang M; Li X; Kim YG; Nunez G; Gupta D; Dziarski R. 2009. PGLYRP-2 and Nod2 are both required for peptidoglycan-induced arthritis and local inflammation. Cell Host Microbe 5(2):137-50. [PubMed: 19218085]  [MGI Ref ID J:178054]

Shaw MH; Reimer T; Sanchez-Valdepenas C; Warner N; Kim YG; Fresno M; Nunez G. 2009. T cell-intrinsic role of Nod2 in promoting type 1 immunity to Toxoplasma gondii. Nat Immunol 10(12):1267-74. [PubMed: 19881508]  [MGI Ref ID J:157739]

Shaw PJ; Barr MJ; Lukens JR; McGargill MA; Chi H; Mak TW; Kanneganti TD. 2011. Signaling via the RIP2 Adaptor Protein in Central Nervous System-Infiltrating Dendritic Cells Promotes Inflammation and Autoimmunity. Immunity 34(1):75-84. [PubMed: 21236705]  [MGI Ref ID J:168072]

Shimada K; Chen S; Dempsey PW; Sorrentino R; Alsabeh R; Slepenkin AV; Peterson E; Doherty TM; Underhill D; Crother TR; Arditi M. 2009. The NOD/RIP2 pathway is essential for host defenses against Chlamydophila pneumoniae lung infection. PLoS Pathog 5(4):e1000379. [PubMed: 19360122]  [MGI Ref ID J:162694]

Smith P; Siddharth J; Pearson R; Holway N; Shaxted M; Butler M; Clark N; Jamontt J; Watson RP; Sanmugalingam D; Parkinson SJ. 2012. Host genetics and environmental factors regulate ecological succession of the mouse colon tissue-associated microbiota. PLoS One 7(1):e30273. [PubMed: 22272321]  [MGI Ref ID J:184305]

Theivanthiran B; Batra S; Balamayooran G; Cai S; Kobayashi K; Flavell RA; Jeyaseelan S. 2012. NOD2 signaling contributes to host defense in the lungs against Escherichia coli infection. Infect Immun 80(7):2558-69. [PubMed: 22547547]  [MGI Ref ID J:186675]

Vaishnava S; Behrendt CL; Ismail AS; Eckmann L; Hooper LV. 2008. Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface. Proc Natl Acad Sci U S A 105(52):20858-63. [PubMed: 19075245]  [MGI Ref ID J:169662]

Wolf AJ; Arruda A; Reyes CN; Kaplan AT; Shimada T; Shimada K; Arditi M; Liu G; Underhill DM. 2011. Phagosomal degradation increases TLR access to bacterial ligands and enhances macrophage sensitivity to bacteria. J Immunol 187(11):6002-10. [PubMed: 22031762]  [MGI Ref ID J:179760]

Zeuthen LH; Fink LN; Frokiaer H. 2008. Toll-like receptor 2 and nucleotide-binding oligomerization domain-2 play divergent roles in the recognition of gut-derived lactobacilli and bifidobacteria in dendritic cells. Immunology 124(4):489-502. [PubMed: 18217947]  [MGI Ref ID J:142781]

Zigmond E; Varol C; Farache J; Elmaliah E; Satpathy AT; Friedlander G; Mack M; Shpigel N; Boneca IG; Murphy KM; Shakhar G; Halpern Z; Jung S. 2012. Ly6C(hi) Monocytes in the Inflamed Colon Give Rise to Proinflammatory Effector Cells and Migratory Antigen-Presenting Cells. Immunity 37(6):1076-90. [PubMed: 23219392]  [MGI Ref ID J:191054]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   23-AUG-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.

Payment Terms and Conditions

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.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Use restrictions apply, see Policy on Licensing and Use Restrictions.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

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.

No Liability

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.