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Molecular and Cellular Biology, August 2002, p. 5296-5307, Vol. 22, No. 15
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.15.5296-5307.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Overlapping and Unique Roles for C-Terminal Binding Protein 1 (CtBP1) and CtBP2 during Mouse Development.

Program in Developmental Biology and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98108,¹ Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260²

Received 25 February 2002/ Returned for modification 15 April 2002/ Accepted 2 May 2002

The C-terminal binding protein (CtBP) family of proteins has been linked to multiple biological processes through their association with numerous transcription factors. We generated mice harboring mutations in both Ctbp1 and Ctbp2 to address the in vivo function of CtBPs during vertebrate development. Ctbp1 mutant mice are small but viable and fertile, whereas Ctbp2-null mice show defects in axial patterning and die by E10.5 due to aberrant extraembryonic development. Mice harboring various combinations of Ctbp1 and Ctbp2 mutant alleles exhibit dosage-sensitive defects in a wide range of developmental processes. The strong genetic interaction, as well as transcription assays with CtBP-deficient cells, indicates that CtBPs have overlapping roles in regulating gene expression. We suggest that the observed phenotypes reflect the large number of transcription factors whose activities are compromised in the absence of CtBP.

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