{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:52:28Z","timestamp":1790805148962,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,11,7]],"date-time":"2018-11-07T00:00:00Z","timestamp":1541548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA143971"],"award-info":[{"award-number":["CA143971"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italian Telethon","award":["GGP15051"],"award-info":[{"award-number":["GGP15051"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Amylo-\u03b1-1,6-glucosidase,4-\u03b1-glucanotransferase (AGL) is an enzyme primarily responsible for glycogen debranching. Germline mutations lead to glycogen storage disease type III (GSDIII). We recently found AGL to be a tumor suppressor in xenograft models of human bladder cancer (BC) and low levels of AGL expression in BC are associated with poor patient prognosis. However, the impact of low AGL expression on the susceptibility of normal bladder to carcinogenesis is unknown. We address this gap by developing a germline Agl knockout (Agl\u2212\/\u2212) mouse that recapitulates biochemical and histological features of GSDIII. Agl\u2212\/\u2212 mice exposed to N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) had a higher BC incidence compared with wild-type mice (Agl+\/+). To determine if the increased BC incidence observed was due to decreased Agl expression in the urothelium specifically, we developed a urothelium-specific conditional Agl knockout (Aglcko) mouse using a Uroplakin II-Cre allele. BBN-induced carcinogenesis experiments repeated in Aglcko mice revealed that Aglcko mice had a higher BC incidence than control (Aglfl\/fl) mice. RNA sequencing revealed that tumors from Agl\u2212\/\u2212 mice had 19 differentially expressed genes compared with control mice. An \u2018Agl Loss\u2019 gene signature was developed and found to successfully stratify normal and tumor samples in two BC patient datasets. These results support the role of AGL loss in promoting carcinogenesis and provide a rationale for evaluating Agl expression levels, or Agl Loss gene signature scores, in normal urothelium of populations at risk of BC development such as older male smokers.<\/jats:p>","DOI":"10.1093\/carcin\/bgy139","type":"journal-article","created":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T21:13:45Z","timestamp":1541193225000},"page":"194-201","source":"Crossref","is-referenced-by-count":6,"title":["Elucidating the role of Agl in bladder carcinogenesis by generation and characterization of genetically engineered mice"],"prefix":"10.1093","volume":"40","author":[{"given":"Joseph L","family":"Sottnik","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Colorado\u2013Anschutz Medical Campus, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vandana","family":"Mallaredy","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Colorado\u2013Anschutz Medical Campus, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Chauca-Diaz","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Colorado\u2013Anschutz Medical Campus, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Ritterson Lew","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Colorado\u2013Anschutz Medical Campus, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Owens","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Colorado\u2013Anschutz Medical Campus, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-8641","authenticated-orcid":false,"given":"Garrett M","family":"Dancik","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Eastern Connecticut State University, Willimantic, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Pagliarani","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience and Mental Health, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Lucchiari","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience and Mental Health, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Moggio","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience and Mental Health, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Ripolone","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Diseases Unit, Department of Neuroscience and Mental Health, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo P","family":"Comi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, and Neurology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Henry F","family":"Frierson","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia, Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Clouthier","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Biology, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Theodorescu","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Colorado\u2013Anschutz Medical Campus, Aurora, CO, USA"},{"name":"Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,11,7]]},"reference":[{"key":"2019092006512317200_CIT0001","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21442","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA. 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