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Molecular and Cellular Biology, October 2000, p. 7292-7299, Vol. 20, No. 19
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

C/EBPbeta , When Expressed from the C/ebpalpha Gene Locus, Can Functionally Replace C/EBPalpha in Liver but Not in Adipose Tissue

Shih-Shun Chen,1 Jin-Feng Chen,1 Peter F. Johnson,2 Vijayakumar Muppala,1 and Ying-Hue Lee1,*

Laboratory of Molecular Pathology, Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan,1 and Eukaryotic Transcriptional Regulation Section, Regulation of Cell Growth Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 217022

Received 10 April 2000/Returned for modification 6 June 2000/Accepted 21 June 2000

Knockout of C/EBPalpha causes a severe loss of liver function and, subsequently, neonatal lethality in mice. By using a gene replacement approach, we generated a new C/EBPalpha -null mouse strain in which C/EBPbeta , in addition to its own expression, substituted for C/EBPalpha expression in tissues. The homozygous mutant mice C/ebpalpha beta /beta are viable and fertile and show none of the overt liver abnormalities found in the previous C/EBPalpha -null mouse line. Levels of hepatic PEPCK mRNA are not different between C/ebpalpha beta /beta and wild-type mice. However, despite their normal growth rate, C/ebpalpha beta /beta mice have markedly reduced fat storage in their white adipose tissue (WAT). Expression of two adipocyte-specific factors, adipsin and leptin, is significantly reduced in the WAT of C/ebpalpha beta /beta mice. In addition, expression of the non-adipocyte-specific genes for transferrin and cysteine dioxygenase is reduced in WAT but not in liver. Our study demonstrates that when expressed from the C/ebpalpha gene locus, C/EBPbeta can act for C/EBPalpha to maintain liver functions during development. Moreover, our studies with the C/ebpalpha beta /beta mice provide new insights into the nonredundant functions of C/EBPalpha and C/EBPbeta on gene regulation in WAT.

* Corresponding author. Mailing address: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan. Phone: 886-2-26517983. Fax: 886-2-26517983. E-mail: mbying{at}ccvax.sinica.edu.tw.

Molecular and Cellular Biology, October 2000, p. 7292-7299, Vol. 20, No. 19
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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