C/EBPbeta, when expressed from the C/ebpalpha gene locus, can functionally replace C/EBPalpha in liver but not in adipose tissue.
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.
Chen
S S
SS
Laboratory of Molecular Pathology, Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
Chen
J F
JF
Johnson
P F
PF
Muppala
V
V
Lee
Y H
YH
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins; D002678:Chimera; D011416:Complement Factor D; D003433:Crosses, Genetic; D050558:Cysteine Dioxygenase; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D049308:Dioxygenases; D005260:Female; D005298:Fertility; D005786:Gene Expression Regulation; D005838:Genotype; D020738:Leptin / Q000096:biosynthesis / Q000235:genetics; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D017093:Liver Failure / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D009928:Organ Specificity; D010105:Oxygenases / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000502:physiology; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D014168:Transferrin / Q000096:biosynthesis / Q000235:genetics
D001786:Blood Glucose; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D020738:Leptin; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014168:Transferrin; D010105:Oxygenases; D049308:Dioxygenases; D050558:Cysteine Dioxygenase; D012697:Serine Endopeptidases; D011416:Complement Factor D; C493491:complement factor D, mouse