caa a22 4500 475770978 CHVBK 20180406123617.0 cr unu---uuuuu 170329e20000101xx s 000 0 eng 10.1007/s001250050016 doi (NATIONALLICENCE)springer-10.1007/s001250050016 Cloning of cDNA and the gene encoding human hepatocyte nuclear factor (HNF)-3 β and mutation screening in Japanese subjects with maturity-onset diabetes of the young [Elektronische Daten] [S. Yamada, Q. Zhu, Y. Aihara, H. Onda, Z. Zhang, L. Yu, L. Jin, Y. -J. Si, H. Nishigori, H. Tomura, I. Inoue, A. Morikawa, K. Yamagata, T. Hanafusa, Y. Matsuzawa, J. Takeda] Abstract : Aims/hypothesis. Molecular defects of the genes for transcription factors, hepatocyte nuclear factor (HNF)-4α, HNF-1α, HNF-1β and insulin promoter factor-1 cause maturity-onset diabetes of the young (MODY1, 3, 5, and 4, respectively). This suggests the HNF-related transcription cascade is important in insulin secretion which is induced by glucose. These genes and the gene encoding glycolytic enzyme glucokinase (MODY2) are, however, responsible for only 15-20 % of cases of MODY in the Japanese. Searching for a novel form of MODY in this population, we cloned a new candidate gene encoding human HNF-3β, a winged helix transcription factor, which also belongs to the same HNF-transcription cascade.¶Methods. The cDNA clone for human HNF-3β was isolated from a liver cDNA library. The gene was also cloned from a genomic library and its organization and chromosomal localization were determined. We screened 68 Japanese subjects with MODY/early-onset diabetes for mutations in this gene.¶Results. Human HNF-3β is composed of 457 amino acids. The human gene, which was mapped to the segment 30 cR from SHGC-37 039 on chromosome 20 p by radiation hybrid mapping, spans approximately 4.5 kb and consists of three exons. Direct sequencing of the exons and flanking regions identified one missense mutation A328 V and seven polymorphisms, although the functional significance of the mutation in the pathogenesis of diabetes is not known.¶Conclusion/interpretation. The characterization of the structure of the HNF-3β gene and its mapping in the framework of markers will be helpful in genetic studies of the various forms of diabetes mellitus. [Diabetologia (2000) 43: 121-124] Springer-Verlag Berlin Heidelberg, 2000 Keywords HNF-cascade, gene expression, insulin secretion, mutation, genetics nationallicence Yamada S. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut Zhu Q. Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan, JP aut Aihara Y. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut Onda H. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut Zhang Z. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut Yu L. Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan, JP aut Jin L. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut Si Y. -J Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut Nishigori H. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut Tomura H. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut Inoue I. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut Morikawa A. Department of Paediatrics, School of Medicine, Gunma University, Gunma, Japan, JP aut Yamagata K. Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan, JP aut Hanafusa T. Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan, JP aut Matsuzawa Y. Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan, JP aut Takeda J. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut https://doi.org/10.1007/s001250050016 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250050016 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yamada S. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Zhu Q. Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan, JP aut NATIONALLICENCE 700 1- Aihara Y. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Onda H. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Zhang Z. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Yu L. Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan, JP aut NATIONALLICENCE 700 1- Jin L. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Si Y. -J Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Nishigori H. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Tomura H. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Inoue I. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Morikawa A. Department of Paediatrics, School of Medicine, Gunma University, Gunma, Japan, JP aut NATIONALLICENCE 700 1- Yamagata K. Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan, JP aut NATIONALLICENCE 700 1- Hanafusa T. Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan, JP aut NATIONALLICENCE 700 1- Matsuzawa Y. Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan, JP aut NATIONALLICENCE 700 1- Takeda J. Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, JP aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer