{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:30:43Z","timestamp":1791293443502,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The biochemical mechanism by which mutations in nucleotide-binding oligomerization domain containing 2 (NOD2) cause Blau syndrome is unknown. Several studies have examined the effect of mutations associated with Blau syndrome in vitro, but none has looked at the implication of the mutations in vivo. To test the hypothesis that mutated NOD2 causes alterations in signaling pathways downstream of NOD2, we created a Nod2 knock-in mouse carrying the most common mutation seen in Blau syndrome, R314Q (corresponding to R334Q in humans). The endogenous regulatory elements of mouse Nod2 were unaltered. R314Q mice showed reduced cytokine production in response to i.p. and intravitreal muramyl dipeptide (MDP). Macrophages from R314Q mice showed reduced NF-\u03baB and IL-6 responses, blunted phosphorylation of MAPKs, and deficient ubiquitination of receptor-interacting protein 2 in response to MDP. R314Q mice expressed a truncated 80-kDa form of NOD2 that was most likely generated by a posttranslational event because there was no evidence for a stop codon or alternative splicing event. Human macrophages from two patients with Blau syndrome also showed a reduction of both cytokine production and phosphorylation of p38 in response to MDP, indicating that both R314Q mice and cells from patients with Blau syndrome show reduced responses to MDP. These data indicate that the R314Q mutation when studied with the Nod2 endogenous regulatory elements left intact is associated with marked structural and biochemical changes that are significantly different from those observed from studies of the mutation using overexpression, transient transfection systems.<\/jats:p>","DOI":"10.4049\/jimmunol.1402330","type":"journal-article","created":{"date-parts":[[2014,11,27]],"date-time":"2014-11-27T05:54:44Z","timestamp":1417067684000},"page":"349-357","source":"Crossref","is-referenced-by-count":45,"title":["Blau Syndrome\u2013Associated <i>Nod2<\/i> Mutation Alters Expression of Full-Length NOD2 and Limits Responses to Muramyl Dipeptide in Knock-in Mice"],"prefix":"10.1093","volume":"194","author":[{"given":"Jae","family":"Dugan","sequence":"first","affiliation":[{"name":"Portland Veterans Affairs Medical Center , Portland, OR 97239"},{"name":"Department of Medicine, Oregon Health and Sciences University , Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center , Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Snow","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center , Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center , Portland, OR 97239"},{"name":"Department of Ophthalmology, Oregon Health and Sciences University , Portland, OR 97239"},{"name":"Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University , Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Oregon Health and Sciences University , Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brieanna","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Oregon Health and Sciences University , Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W","family":"Carr","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center , Portland, OR 97239"},{"name":"Department of Medicine, Oregon Health and Sciences University , Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Rose","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, DuPont Hospital for Children , Wilmington, DE 19803"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Rosenbaum","sequence":"additional","affiliation":[{"name":"Department of Medicine, Oregon Health and Sciences University , Portland, OR 97239"},{"name":"Department of Ophthalmology, Oregon Health and Sciences University , Portland, OR 97239"},{"name":"Legacy Devers Eye Institute , Portland, OR 97210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P","family":"Davey","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center , Portland, OR 97239"},{"name":"Department of Medicine, Oregon Health and Sciences University , Portland, OR 97239"},{"name":"Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University , Portland, OR 97239"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,1,1]]},"reference":[{"key":"2025031310013224400_r1","doi-asserted-by":"crossref","first-page":"8869","DOI":"10.1074\/jbc.C200651200","article-title":"Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection","volume":"278","author":"Girardin","year":"2003","journal-title":"J. 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