title: Functional defect of truncated hepatocyte nuclear factor-1alpha (G554fsX556) associated with maturity-onset diabetes of the young.
abstract: A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1alpha (HNF-1alpha) encoding a truncated HNF-1alpha (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). The wild-type and mutant HNF-1alpha proteins were expressed by in vitro transcription and translation (TNT) assay and by transfection in HeLa cells. The wild-type and mutant HNF-1alpha could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). However, the transactivation activities of mutant HNF-1alpha on human GLUT2 and rat L-type pyruvate kinase (L-PK) promoters in HeLa cells determined by luciferase reporter assay were reduced to approximately 55-60% of the wild-type protein. These results suggested that the functional defect of novel truncated HNF-1alpha (G554fsX556) on the transactivation of its target-gene promoters would account for the beta-cell dysfunction associated with the pathogenesis of MODY.
authors.affiliation: Department of Physiology, Mahidol University, Bangkok, Thailand. S_kooptiwut@hotmail.com
authors.forename: Suwattanee
authors.initials: S
authors.lastname: Kooptiwut
authors.forename: Jatuporn
authors.initials: J
authors.lastname: Sujjitjoon
authors.forename: Nattachet
authors.initials: N
authors.lastname: Plengvidhya
authors.forename: Watip
authors.initials: W
authors.lastname: Boonyasrisawat
authors.forename: Nalinee
authors.initials: N
authors.lastname: Chongjaroen
authors.forename: Prapapron
authors.initials: P
authors.lastname: Jungtrakoon
authors.forename: Namoiy
authors.initials: N
authors.lastname: Semprasert
authors.forename: Hiroto
authors.initials: H
authors.lastname: Furuta
authors.forename: Kishio
authors.initials: K
authors.lastname: Nanjo
authors.forename: Napatawn
authors.initials: N
authors.lastname: Banchuin
authors.forename: Pa-thai
authors.initials: PT
authors.lastname: Yenchitsomanus