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Updated: Sep 26, 2026

Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Rescue of MODY-1 by agonist ligands of hepatocyte nuclear factor-4alpha
Rachel Hertz1, Nadav Ben-Haim, Anca D Petrescu
1Department of Human Nutrition and Metabolism, Hebrew University Medical School, Jerusalem 91120, Israel.
Abstract:
Missense mutations of the ligand binding domain of hepatocyte nuclear factor (HNF)-4alpha result in maturity onset diabetes of the young (MODY)-1. We show here that MODY-1 as well as Gln-185 missense mutants of the ligand binding domain of HNF-4alpha fail to transactivate transcription of HNF-4alpha-responsive genes. Defective transactivation by these mutants is accounted for by their reduced binding affinities for fatty acyl agonist ligands of HNF-4alpha. These mutants may be rescued by exogenous fatty acid agonist ligands of HNF-4alpha, yielding transcriptional activities in the wild type range. The effect of added ligands is synergistic with that of transcriptional coactivators of HNF-4alpha. These findings may indicate the means for treating selected MODY-1 subjects with HNF-4alpha agonist nutrients and drugs.
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