B6.129S1-Nod2^tm1Flv/J

Stock number: 005763
Product name: Nod2 KO
Research areas: Cell Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These Nod2 knock-out mice are susceptible to oral bacterial challenge and may be useful in studies of Crohn's disease and other inflammatory bowel diseases.

Detailed 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.

Allele

Symbol: Nod2^tm1Flv
Name: targeted mutation 1, Richard A Flavell
MGI accession ID: MGI:3529594
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Nod2
Marker name: nucleotide-binding oligomerization domain containing 2
Chromosome: 8
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
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.