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Molecular and Cellular Biology, November 2004, p. 9744-9751, Vol. 24, No. 22
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.22.9744-9751.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Essential Requirement of CCAAT/Enhancer Binding Proteins in Embryogenesis

Max Delbrueck Center for Molecular Medicine, Berlin, Germany

Received 31 March 2004/ Returned for modification 14 May 2004/ Accepted 19 August 2004

The CCAAT/enhancer binding proteins C/EBP and C/EBPß are related transcription factors that are important for the function of various organs in the postnatal mouse. Gene replacement and tissue culture experiments have suggested partial redundancy of both transcription factors. Here we show that mouse embryos deficient of both C/EBP and C/EBPß (C/EBPß^–/–) die between embryonic day 10 (E10) and E11 and display defective placentas. In situ hybridization revealed that C/EBP and C/EBPß are coexpressed in the chorionic plate at E9.5 and later in the trophoblasts of the labyrinthine layer. In C/EBPß^–/– placentas, allantoic blood vessels invaded the chorion; however, vessel expansion and development of the labyrinthine layer was impaired. Furthermore, a single copy of either C/EBP in the absence of C/EBPß or C/EBPß in the absence of C/EBP is sufficient to complete development, suggesting complementation of these C/EBPs during embryogenesis. A single copy of C/EBP in the absence of C/EBPß, however, fails to rescue survival after birth, suggesting haploinsufficiency of C/EBP in newborns. Our data thus reveal novel essential, redundant, and dosage dependent functions of C/EBPs.

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