{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T08:31:27Z","timestamp":1768725087740,"version":"3.49.0"},"reference-count":33,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in the hepatocyte nuclear factor (HNF)-1\u03b2 lead to type 5 maturity-onset diabetes of the young (MODY5). HNF-1\u03b2 forms a homodimer or a heterodimer with HNF-1\u03b1 and regulates various target genes. HNF-1\u03b2 mutations are rare, and no functional analysis has been performed in conjunction with HNF-1\u03b1. HNF-1\u03b2 is expressed in the liver and biliary system and controls liver-specific and bile acid-related genes. Moreover, liver-specific Hnf-1\u03b2 knockout mice present with severe jaundice. However, no patients with HNF-1\u03b2 mutations have biliary manifestations. In this report, we found a novel missense mutation in the HNF-1\u03b2 gene in a patient with neonatal cholestasis and liver dysfunction together with the common features of MODY5. Functional analysis revealed that the mutant HNF-1\u03b2 had diminished transcriptional activity by loss of the DNA binding activity. The mutant had a promoter-specific dominant-negative transcriptional effect on wild-type HNF-1\u03b2 and inhibited its DNA binding. Moreover, the mutant had a promoter- and cell-specific transcriptional repressive effect on HNF-1\u03b1 and a promoter-specific inhibitory effect on HNF-1\u03b1 DNA binding. From these results, we considered that the different phenotype of patients with HNF-1\u03b2 mutations might be caused by the different HNF-1\u03b2 activity in conjunction with the different repression of HNF-1\u03b1 activity in selected promoters and tissues.<\/jats:p>","DOI":"10.1210\/jc.2003-031308","type":"journal-article","created":{"date-parts":[[2004,3,5]],"date-time":"2004-03-05T01:53:04Z","timestamp":1078451584000},"page":"1369-1378","source":"Crossref","is-referenced-by-count":37,"title":["Promoter-Specific Repression of Hepatocyte Nuclear Factor (HNF)-1\u03b2 and HNF-1\u03b1 Transcriptional Activity by an HNF-1\u03b2 Missense Mutant Associated with Type 5 Maturity-Onset Diabetes of the Young with Hepatic and Biliary Manifestations"],"prefix":"10.1210","volume":"89","author":[{"given":"Sachiko","family":"Kitanaka","sequence":"first","affiliation":[{"name":"Department of Pediatrics (S.K., Y.M., Y.H., T.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655"},{"name":"Japan Health Sciences Foundation (S.K.), Tokyo 103-0001, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Miki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (S.K., Y.M., Y.H., T.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhide","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (S.K., Y.M., Y.H., T.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (S.K., Y.M., Y.H., T.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 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