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Genes & Alleles

Nod2;   Nod2tm1Flv;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Targeted Mutation Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Donating Investigator Richard Flavell,   Yale University School of Medicine Generation ?+N1F5 (30-APR-08)

Strain 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.

Strain 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 resulting heterozygotes were backcrossed to C57BL/6 mice 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.

Mammalian Phenotype Terms assigned by genotype The following phenotype information may relate to a genetic background differing from this JAX® Mice strain. Nod2tm1Flv/Nod2tm1Flv         involves: 129S1/Sv * C57BL/6 immune system phenotype abnormal interleukin physiology (MGI Ref ID J:96035) the synergistic effect of bacterial muramyl dipeptide and TLR ligands on the production of IL6 and IL12 is absent in mutant macrophages altered susceptibility to infection (MGI Ref ID J:96035) homozygotes are more susceptible to Listeria monocytogenes infection via intragastric exposure but not via intraperitoneal or intravenous exposure however, no signs of intestinal inflammation and no difference in susceptibility to dextran sulfate induced colitis are seen decreased IgG level (MGI Ref ID J:96035) 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 decreased susceptibility to endotoxin shock (MGI Ref ID J:96035) homozygotes are resistant to endotoxin shock produced by LPS following bacterial muramyl dipeptide priming but not to endotoxin shock produced by LPS alone

Gene & Allele Details

Allele Symbol		Nod2tm1Flv
Allele Name		targeted mutation 1, Richard A Flavell
Common Name(s)		Nod2-;
Mutation Made By		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]

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Genotyping Protocols

Nod2^tm1Flv

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.
Diet Information	LabDiet® 5K52/5K67

Additional Web Information

Congenic Nomenclature

Animal Health Reports

Room Number           AX11

Research Applications

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

Cell Biology Research
Signal Transduction

Hematological Research
Immunological Defects

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

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

References

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

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Price and Supply Information

Strain Name:	B6.129S1-Nod2tm1Flv/J
Stock Number:	005763

Price Details

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Supply Details

Standard Supply	Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.
Supply Notes	Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.
Licensing	See General Terms and Conditions below for Licensing and Use Restrictions
Control Information	View Control Information in Strain Details.

General Terms and Conditions

View JAX^® Mice & Services Conditions of Use.

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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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