caa a22 4500 475772318 CHVBK 20180406123620.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1007/s001250051338 doi (NATIONALLICENCE)springer-10.1007/s001250051338 R127W-HNF-4α is a loss of function mutation but not a rare polymorphism and causes Type II diabetes in a Japanese family with MODY1 [Elektronische Daten] [Q. Yang, K. Yamagata, K. Yamamoto, Y. Cao, J. Miyagawa, A. Fukamizu, T. Hanafusa, Y. Matsuzawa] Abstract : Aims/hypothesis. Mutations in the hepatocyte nuclear factor (HNF)-4 α gene cause the type 1 form of maturity-onset diabetes of the young (MODY1). The R127W mutation is a missense mutation located in the T-box region of HNF-4α that was first identified in a Japanese family with MODY. We have examined the functional properties of this mutation in order to clarify the molecular basis of MODY1.¶Methods. The intracellular localisation, DNA binding ability, transactivation activity and functional synergism with the coactivator CREB-binding protein (CBP) of R127W-HNF-4α were investigated.¶Results. The nuclear import and functional synergy with CBP of R127W-HNF-4α were normal. The DNA binding ability of the mutant was decreased as was its transcriptional activation of the HNF-1 α and L-type pyruvate kinase (PKL) genes.¶Conclusion/interpretation. The R127W mutation seems to be a loss-of-function mutation. [Diabetologia (2000) 43: 520-524] Springer-Verlag Berlin Heidelberg, 2000 Keywords MODY, HNF-4α, HNF-1α, L-type pyruvate kinase, insulin nationallicence Yang Q. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan, JP aut Yamagata K. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan, JP aut Yamamoto K. The Department of General Medicine, Osaka University Hospital, Osaka, Japan, JP aut Cao Y. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan, JP aut Miyagawa J. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan, JP aut Fukamizu A. Centre for Tsukuba Advanced Research Alliance, Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan, JP aut Hanafusa T. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan, JP aut Matsuzawa Y. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan, JP aut https://doi.org/10.1007/s001250051338 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051338 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yang Q. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan, JP aut NATIONALLICENCE 700 1- Yamagata K. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan, JP aut NATIONALLICENCE 700 1- Yamamoto K. The Department of General Medicine, Osaka University Hospital, Osaka, Japan, JP aut NATIONALLICENCE 700 1- Cao Y. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan, JP aut NATIONALLICENCE 700 1- Miyagawa J. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan, JP aut NATIONALLICENCE 700 1- Fukamizu A. Centre for Tsukuba Advanced Research Alliance, Institute of Applied Biochemistry, University of Tsukuba, Ibaraki, Japan, JP aut NATIONALLICENCE 700 1- Hanafusa T. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan, JP aut NATIONALLICENCE 700 1- Matsuzawa Y. The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan, JP aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer