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Mol Cell Biol, July 1998, p. 4245-4251, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Targeted Disruption of the Gene Encoding Hepatocyte Nuclear Factor 3gamma Results in Reduced Transcription of Hepatocyte-Specific Genes

Klaus H. Kaestner,1 * Holger Hiemisch,2 and Günther Schütz2

Department of Genetics, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104-6145,1 and Division of Molecular Biology of the Cell I, German Cancer Research Centre, D-69120 Heidelberg, Germany2

Received 5 February 1998/Returned for modification 2 April 1998/Accepted 22 April 1998

The winged helix transcription factor hepatocyte nuclear factor 3gamma (HNF3gamma ) is expressed in embryonic endoderm and its derivatives liver, pancreas, stomach, and intestine, as well as in testis and ovary. We have generated mice carrying an Hnf3g-lacZ fusion which deletes most of the HNF3gamma coding sequence as well as 5.5 kb of 3' flanking region. Mice homozygous for the mutation are fertile, develop normally, and show no morphological defects. The mild phenotype change of the Hnf3g-/- mice can be explained in part by an upregulation of HNF3alpha and HNF3beta in the liver of the mutant animals. Analysis of steady-state mRNA levels as well as transcription rates showed that levels of expression of several HNF3 target genes (phosphoenolpyruvate carboxykinase, transferrin, tyrosine aminotransferase) were reduced by 50 to 70%, indicating that HNF3gamma is an important activator of these genes in vivo.

* Corresponding author. Mailing address: Department of Genetics, University of Pennsylvania Medical School, 415 Curie Blvd., Philadelphia, PA 19104-6145. Phone: (215) 898-8759. Fax: (215) 573-5892. E-mail: kaestner{at}mail.med.upenn.edu.

Mol Cell Biol, July 1998, p. 4245-4251, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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