{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:32:18Z","timestamp":1784179938353,"version":"3.55.0"},"reference-count":25,"publisher":"The Company of Biologists","issue":"12","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":642,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK107886"],"award-info":[{"award-number":["DK107886"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI005184"],"award-info":[{"award-number":["AI005184"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37 GM066759"],"award-info":[{"award-number":["R37 GM066759"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) is a member of the basic helix-loop-helix\/PER-ARNT-SIM (bHLH\/PAS) transcription factor family. ARNT2 heterodimerizes with several members of the family, including single-minded homolog-1 (SIM1) and neuronal PAS domain protein 4 (NPAS4), primarily in neurons of the central nervous system. We screened 64,424 third-generation germline mutant mice derived from N-ethyl-N-nitrosourea (ENU)-mutagenized great-grandsires for weight abnormalities. Among 17 elevated body weight phenotypes identified and mapped, one strongly correlated with an induced missense mutation in Arnt2 using a semidominant model of inheritance. Causation was confirmed by CRISPR\/Cas9 gene targeting to recapitulate the original ENU allele, specifying Arg74Cys (R74C). The CRISPR\/Cas9-targeted (Arnt2R74C\/R74C) mice demonstrated hyperphagia and increased adiposity as well as hepatic steatosis and abnormalities in glucose homeostasis. The mutant ARNT2 protein showed decreased transcriptional activity when coexpressed with SIM1. These findings establish a requirement for ARNT2-dependent genes in the maintenance of the homeostatic feeding response, necessary for prevention of obesity and obesity-related diseases.<\/jats:p>","DOI":"10.1242\/dmm.035451","type":"journal-article","created":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T21:05:14Z","timestamp":1545167114000},"source":"Crossref","is-referenced-by-count":8,"title":["A viable hypomorphic <i>Arnt2<\/i> mutation causes hyperphagic obesity, diabetes and hepatic steatosis"],"prefix":"10.1242","volume":"11","author":[{"given":"Emre E.","family":"Turer","sequence":"first","affiliation":[{"name":"Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8505, USA"},{"name":"Department of Internal Medicine, Division of Gastroenterology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8505\u2008USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"San 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Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8505, USA"},{"name":"Department of Internal Medicine, Division of Gastroenterology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8505\u2008USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Li","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Tang","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Zang","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Braden","family":"Hayse","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8505, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bret","family":"Evers","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8505\u2008USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Zhan","sequence":"additional","affiliation":[{"name":"Center for the Genetics of Host Defense, University of Texas Southwestern Medical 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