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PubMed · 10982846

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

S S Chen·J F Chen·P F Johnson·V Muppala·Y H Lee
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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.

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Adipose TissueAnimalsBlood GlucoseCCAAT-Enhancer-Binding ProteinsChimeraComplement Factor DCrosses, GeneticCysteine DioxygenaseDNA-Binding ProteinsDioxygenasesFemaleFertilityGene Expression RegulationGenotypeLeptinLipid MetabolismLiverLiver FailureMaleMiceMice, Inbred C57BLMice, KnockoutNuclear ProteinsOrgan SpecificityOxygenasesPromoter Regions, GeneticRNA, MessengerRecombinant Fusion ProteinsSerine EndopeptidasesTransferrinComparative StudyJournal Article

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S S Chen, J F Chen, P F Johnson, V Muppala, Y H Lee. 2000. C/EBPbeta, when expressed from the C/ebpalpha gene locus, can functionally replace C/EBPalpha in liver but not in adipose tissue.. https://doi.org/10.1128/mcb.20.19.7292-7299.2000

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