title: Genetic variation and activity of mouse Nod2, a susceptibility gene for Crohn's disease.
abstract: Genetic variation in human Nod2 has been associated with susceptibility to Crohn's disease. The mouse Nod2 locus is located at chromosome 8 and composed of 12 exons, 11 of which encode the Nod2 protein. Sequence analysis of Nod2 from 45 different strains of Mus musculus and Mus spretus revealed extensive polymorphism involving all exons of Nod2. Of the 140 polymorphic sites identified, 68 were located in the coding region, of which 28 created amino acid substitutions in Nod2. Expression of mouse Nod2 activated NF-kappaB and conferred responsiveness to bacterial components, an activity that was deficient in mutants corresponding to those associated with susceptibility to Crohn's disease. These studies demonstrate a conserved role for Nod2 in the response to bacterial components and suggest that selective evolutionary pressure exerted by pathogens may have contributed to the high level of variability of Nod2 sequences in both humans and mice.
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ogura
authors.forename: Lisa
authors.initials: L
authors.lastname: Saab
authors.forename: Felicia F
authors.initials: FF
authors.lastname: Chen
authors.forename: Adalberto
authors.initials: A
authors.lastname: Benito
authors.forename: Naohiro
authors.initials: N
authors.lastname: Inohara
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nuñez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D003424:Crohn Disease / Q000235:genetics*; D017931:DNA Primers; D015870:Gene Expression; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D009115:Muridae / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein; D010802:Phylogeny; D011110:Polymorphism, Genetic
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein