{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T01:09:40Z","timestamp":1794100180385,"version":"4.8.0"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T00:00:00Z","timestamp":1296518400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Type I interferons (IFNs) are central regulators of the innate and adaptive immune responses to viral and bacterial infections. Type I IFNs are induced upon cytosolic detection of microbial nucleic acids, including DNA, RNA, and the bacterial second messenger cyclic-di-GMP (c-di-GMP). In addition, a recent study demonstrated that the intracellular bacterial pathogen<jats:italic>Listeria monocytogenes<\/jats:italic>stimulates a type I IFN response due to cytosolic detection of bacterially secreted c-di-AMP. The transmembrane signaling adaptor Sting (Tmem173, Mita, Mpys, Eris) has recently been implicated in the induction of type I IFNs in response to cytosolic DNA and\/or RNA. However, the role of Sting in response to purified cyclic dinucleotides or during<jats:italic>in vivo L. monocytogenes<\/jats:italic>infection has not been addressed. In order to identify genes important in the innate immune response, we have been conducting a forward genetic mutagenesis screen in C57BL\/6 mice using the mutagen<jats:italic>N<\/jats:italic>-ethyl-<jats:italic>N<\/jats:italic>-nitrosourea (ENU). Here we describe a novel mutant mouse strain,<jats:italic>Goldenticket<\/jats:italic>(<jats:italic>Gt<\/jats:italic>), that fails to produce type I IFNs upon<jats:italic>L. monocytogenes<\/jats:italic>infection. By genetic mapping and complementation experiments, we found that<jats:italic>Gt<\/jats:italic>mice harbor a single nucleotide variant (T596A) of<jats:italic>Sting<\/jats:italic>that functions as a null allele and fails to produce detectable protein. Analysis of macrophages isolated from<jats:italic>Gt<\/jats:italic>mice revealed that<jats:italic>Sting<\/jats:italic>is absolutely required for the type I interferon response to both c-di-GMP and c-di-AMP. Additionally,<jats:italic>Sting<\/jats:italic>is required for the response to c-di-GMP and<jats:italic>L. monocytogenes in vivo<\/jats:italic>. Our results provide new functions for<jats:italic>Sting<\/jats:italic>in the innate interferon response to pathogens.<\/jats:p>","DOI":"10.1128\/iai.00999-10","type":"journal-article","created":{"date-parts":[[2010,11,23]],"date-time":"2010-11-23T04:07:46Z","timestamp":1290485266000},"page":"688-694","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":556,"title":["The<i>N<\/i>-Ethyl-<i>N<\/i>-Nitrosourea-Induced<i>Goldenticket<\/i>Mouse Mutant Reveals an Essential Function of<i>Sting<\/i>in the<i>In Vivo<\/i>Interferon Response to<i>Listeria monocytogenes<\/i>and Cyclic Dinucleotides"],"prefix":"10.1128","volume":"79","author":[{"given":"John-Demian","family":"Sauer","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Sotelo-Troha","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"von Moltke","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M.","family":"Monroe","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris S.","family":"Rae","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sky W.","family":"Brubaker","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoru","family":"Hyodo","sequence":"additional","affiliation":[{"name":"Laboratory of Bioorganic Chemistry, Graduate School of Information Science, Nagoya University, Chikusa, Nagoya 464-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Faculty of Engineering, Aichi Institute of Technology, 1247 Yachigusa, Yakusa, Toyota 470-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua J.","family":"Woodward","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Portnoy","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720"},{"name":"School of Public Health, University of California, Berkeley, California 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell E.","family":"Vance","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 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