C/EBPbeta, when expressed from the C/ebpalpha gene locus, can functionally replace C/EBPalpha in liver but not in adipose tissue.

Authors: Chen SS; Chen JF; Johnson PF; Muppala V; Lee YH

Abstract: 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.

Keywords: Adipose Tissue/*metabolism; Animals; Blood Glucose/metabolism; CCAAT-Enhancer-Binding Proteins; Chimera; Complement Factor D; Crosses, Genetic; Cysteine Dioxygenase; DNA-Binding Proteins/biosynthesis/deficiency/*genetics/*physiology; *Dioxygenases; Female; Fertility; *Gene Expression Regulation; Genotype; Leptin/biosynthesis/genetics; Lipid Metabolism; Liver/*metabolism; Liver Failure/*genetics/metabolism/prevention & control; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nuclear Proteins/biosynthesis/deficiency/*genetics/*physiology; Organ Specificity; Oxygenases/biosynthesis/genetics; *Promoter Regions, Genetic; RNA, Messenger/biosynthesis/genetics; Recombinant Fusion Proteins/biosynthesis/physiology; Serine Endopeptidases/biosynthesis/genetics; Transferrin/biosynthesis/genetics
Journal: Molecular and cellular biology
Volume: 20
Issue: 19
Pages: 7292-9
Date: Sept. 13, 2000
PMID: 10982846
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Chen SS, Chen JF, Johnson PF, Muppala V, Lee YH (2000) C/EBPbeta, when expressed from the C/ebpalpha gene locus, can functionally replace C/EBPalpha in liver but not in adipose tissue. Molecular and cellular biology 20: 7292-9.

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