{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T01:27:02Z","timestamp":1772242022496,"version":"3.50.1"},"reference-count":50,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T00:00:00Z","timestamp":1689206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31871192"],"award-info":[{"award-number":["31871192"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82150110"],"award-info":[{"award-number":["82150110"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Hospitals Authority\u2019s Ascent Plan","award":["DFL20221502"],"award-info":[{"award-number":["DFL20221502"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2018M643903"],"award-info":[{"award-number":["2018M643903"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Hepatocyte nuclear factor 1\u03b1 (HNF1\u03b1) plays essential roles in controlling development and metabolism; its mutations are clearly linked to the occurrence of maturity-onset diabetes of the young (MODY3) in humans. Lysine 117 (K117) to glutamic acid (E117) mutation in the HNF1\u03b1 gene has been clinically associated with MODY3, but no functional data on this variant are available. Here, we addressed the role of lysine 117 in HNF1\u03b1 function using a knock-in animal model and site-directed mutagenesis. HNF1\u03b1 K117E homozygous mice exhibited dwarfism, hepatic dysfunction, renal Fanconi syndrome, and progressive wasting syndrome. These phenotypes were very similar to those of mice with complete HNF1\u03b1 deficiency, suggesting that K117 is critical to HNF1\u03b1 functions. K117E homozygotes developed diabetes in the early postnatal period. The relative deficiency of serum insulin levels and the normal response to insulin treatment in homozygous mice were markedly similar to those in the MODY3 disorder in humans. Moreover, K117E heterozygous mutant causes age-dependent glucose intolerance, which is similar to the pathogenesis of MODY3 as well. K117 mutants significantly reduced the overall transactivation and DNA binding capacity of HNF1\u03b1 by disrupting dimerization. Collectively, our findings reveal a previously unappreciated role of POU domain of HNF1\u03b1 in homodimerization and provide important clues for identifying the molecular basis of HNF1\u03b1-related diseases such as MODY3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>HNF1\u03b1 K117E homozygous mice exhibited dwarfism, hepatic dysfunction, renal Fanconi syndrome, and progressive wasting syndrome. K117E homozygotes developed diabetes in the early postnatal period. K117E heterozygous mutant causes age-dependent glucose intolerance, which is similar to the pathogenesis of maturity-onset diabetes of the young. K117 mutants significantly reduced the overall transactivation and DNA binding capacity of HNF1\u03b1 by disrupting dimerization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db22-0672","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T14:59:18Z","timestamp":1689260358000},"page":"1502-1516","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":1,"title":["Lysine 117 Residue Is Essential for the Function of the Hepatocyte Nuclear Factor 1\u03b1"],"prefix":"10.2337","volume":"72","author":[{"given":"Yuan","family":"Chu","sequence":"first","affiliation":[{"name":"1State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, China"},{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Zhao","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian","family":"Liu","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, China"},{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, China"},{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Zhao","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, China"},{"name":"3Department of Hygienic Toxicology and Environmental Hygiene, Tianjin Institute of Environmental and Operational Medicine, Tianjin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sicong","family":"Chen","sequence":"additional","affiliation":[{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shensi","family":"Xiang","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Lu","sequence":"additional","affiliation":[{"name":"4Hepatology and Cancer Biotherapy Ward, Beijing YouAn Hospital, Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofang","family":"Wang","sequence":"additional","affiliation":[{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"},{"name":"5Institute of Life Sciences, He Bei University, Baoding, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Wan","sequence":"additional","affiliation":[{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"},{"name":"6School of Basic Medical Sciences, An Hui Medical University, Hefei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diandian","family":"Dong","sequence":"additional","affiliation":[{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"},{"name":"5Institute of Life Sciences, He Bei University, Baoding, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songhui","family":"Yao","sequence":"additional","affiliation":[{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changyan","family":"Li","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, China"},{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"},{"name":"6School of Basic Medical Sciences, An Hui Medical University, Hefei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronghua","family":"Yin","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, China"},{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangming","family":"Ren","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, China"},{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoming","family":"Yang","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, China"},{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2963-8254","authenticated-orcid":false,"given":"Miao","family":"Yu","sequence":"additional","affiliation":[{"name":"1State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, China"},{"name":"2State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China"},{"name":"5Institute of Life Sciences, He Bei University, Baoding, China"},{"name":"6School of Basic Medical Sciences, An Hui Medical University, Hefei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2023,7,13]]},"reference":[{"key":"2023092018511102900_B1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0092-8674(89)90877-5","article-title":"The liver-specific transcription factor LF-B1 contains a highly diverged homeobox DNA binding domain","volume":"59","author":"Frain","year":"1989","journal-title":"Cell"},{"key":"2023092018511102900_B2","first-page":"47","article-title":"Transcriptional activators in hepatocytes","volume":"1","author":"Johnson","year":"1990","journal-title":"Cell Growth Differ"},{"key":"2023092018511102900_B3","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1101\/gad.2.8.957","article-title":"A liver-specific factor essential for albumin transcription differs between differentiated and dedifferentiated rat hepatoma 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