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Mol Cell Biol, May 1998, p. 3059-3068, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Laron Dwarfism and Non-Insulin-Dependent Diabetes Mellitus in the Hnf-1alpha Knockout Mouse

Ying-Hue Lee,1,2,* Brian Sauer,3 and Frank J. Gonzalez1

Laboratory of Metabolism, National Cancer Institute,1 and Laboratory of Biochemistry and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases,3 National Institutes of Health, Bethesda, Maryland 20892, and Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan2

Received 15 October 1997/Returned for modification 9 December 1997/Accepted 27 January 1998

Mice deficient in hepatocyte nuclear factor 1 alpha (HNF-1alpha ) were produced by use of the Cre-loxP recombination system. HNF-1alpha -null mice are viable but sterile and exhibit a phenotype reminiscent of both Laron-type dwarfism and non-insulin-dependent diabetes mellitus (NIDDM). In contrast to an earlier HNF-1alpha -null mouse line that had been produced by use of standard gene disruption methodology (M. Pontoglio, J. Barra, M. Hadchouel, A. Doyen, C. Kress, J. P. Bach, C. Babinet, and M. Yaniv, Cell 84:575-585, 1996), these mice exhibited no increased mortality and only minimal renal dysfunction during the first 6 months of development. Both dwarfism and NIDDM are most likely due to the loss of expression of insulin-like growth factor I (IGF-I) and lower levels of insulin, resulting in stunted growth and elevated serum glucose levels, respectively. These results confirm the functional significance of the HNF-1alpha regulatory elements that had previously been shown to reside in the promoter regions of both the IGF-I and the insulin genes.

* Corresponding author. Mailing address: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan. Phone: 886-2-6517983. Fax: 886-2-7826085. E-mail: mbying{at}ccvax.sinica.edu.tw.

Mol Cell Biol, May 1998, p. 3059-3068, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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