ISSN:
1432-0428
Keywords:
Keywords MODY, HNF-4α, HNF-1α, L-type pyruvate kinase, insulin.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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]
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s001250051338
