{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:22:03Z","timestamp":1782966123019,"version":"3.54.5"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2679,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DK49564"],"award-info":[{"award-number":["R01 DK49564"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DK70592"],"award-info":[{"award-number":["R01 DK70592"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32 DK07542"],"award-info":[{"award-number":["T32 DK07542"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Predoctoral fellowship from the American Heart Association","award":["0615665T"],"award-info":[{"award-number":["0615665T"]}]},{"name":"Center for Gastroenterology Research on Absorptive and Secretory Processes","award":["P30 DK34928"],"award-info":[{"award-number":["P30 DK34928"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:sec><jats:title\/><jats:p><jats:bold>Niemann-Pick type C (NPC) is a fatal autosomal recessive lipidosis that is characterized by lysosomal storage of cholesterol and glycosphingolipids. Patients exhibit prolonged neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration that generally result in death by the teen years. Most clinical cases are caused by mutations in the<\/jats:bold><jats:bold>NPC1<\/jats:bold><jats:bold>gene. Current mouse models of NPC are not well suited for studying the liver disease due to the rapidly progressing neurological disease. To facilitate study of NPC-associated liver dysfunction, we have developed a novel mouse model using antisense oligonucleotides to ablate NPC1 expression primarily in the liver. Here, we show that the NPC1 knockdown leads to a liver disease phenotype similar to that of patients with NPC and the NPCnih mouse model. Key features include hepatomegaly, lipid storage, elevated serum liver enzymes, and increased apoptosis.<\/jats:bold><jats:bold>Conclusion:<\/jats:bold><jats:bold>This novel NPC1 antisense mouse model will allow delineation of the mechanism by which NPC1 dysfunction leads to liver cell death.<\/jats:bold><\/jats:p><\/jats:sec>","DOI":"10.1002\/hep.22327","type":"journal-article","created":{"date-parts":[[2008,4,25]],"date-time":"2008-04-25T17:46:23Z","timestamp":1209145583000},"page":"1504-1512","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":34,"title":["In vivo antisense oligonucleotide reduction of NPC1 expression as a novel mouse model for Niemann Pick type C\u2013 associated liver disease"],"prefix":"10.1097","volume":"47","author":[{"given":"Victoria M.","family":"Rimkunas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanne M.","family":"Crooke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Liscum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R2-10-20241201","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1034\/j.1399-0004.2003.00147.x","article-title":"NiemannPick disease type C.","volume":"64","author":"Vanier","year":"2003","journal-title":"Clin Genet"},{"key":"R3-10-20241201","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0022-3476(05)81695-6","article-title":"NiemannPick disease type C: diagnosis and outcome in children, with particular reference to liver disease.","volume":"123","author":"Kelly","year":"1993","journal-title":"J Pediatr"},{"key":"R4-10-20241201","first-page":"44","article-title":"Niemannpick disease type C in neonatal cholestasis at a North American Center.","volume":"35","author":"Yerushalmi","year":"2002","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"R5-10-20241201","first-page":"118","article-title":"Genetic heterogeneity in NiemannPick C disease: a study using somatic cell hybridization and linkage analysis.","volume":"58","author":"Vanier","year":"1996","journal-title":"Am J Hum Genet"},{"key":"R6-10-20241201","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3109\/15513818909022387","article-title":"Progressive neonatal liver failure due to type C NiemannPick disease.","volume":"9","author":"Rutledge","year":"1989","journal-title":"Pediatr Pathol"},{"key":"R7-10-20241201","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/00004836-199209000-00013","article-title":"Liver failure and the seablue histiocyteadult NiemannPick disease. 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