Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome

Cell. 1996 Feb 23;84(4):575-85. doi: 10.1016/s0092-8674(00)81033-8.


HNF1 is a transcriptional activator of many hepatic genes including albumin, alpha1-antitrypsin, and alpha- and beta-fibrinogen. It is related to the homeobox gene family and is predominantly expressed in liver and kidney. Mice lacking HNF1 fail to thrive and die around weaning after a progressive wasting syndrome with a marked liver enlargement. The transcription rate of genes like albumin and alpha1-antitrypsin is reduced, while the gene coding for phenylalanine hydroxylase is totally silent, giving rise to phenylketonuria. Mutant mice also suffer from severe Fanconi syndrome caused by renal proximal tubular dysfunction. The resulting massive urinary glucose loss leads to energy and water wasting. HNF1-deficient mice may provide a model for human renal Fanconi syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • DNA-Binding Proteins*
  • Embryo, Mammalian / physiology
  • Fanconi Syndrome / genetics
  • Fanconi Syndrome / physiopathology*
  • Gene Expression / physiology
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Heterozygote
  • Liver Diseases / genetics
  • Liver Diseases / pathology
  • Liver Diseases / physiopathology*
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Nuclear Proteins / physiology*
  • Phenylketonurias / genetics
  • Phenylketonurias / physiopathology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic / physiology


  • DNA-Binding Proteins
  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • Hnf1b protein, mouse
  • Nuclear Proteins
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta