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

Abstract

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.

We thank Joseph Keilic, Peter Mueting-Nelsen, and Philip Corrin for help with genotyping; Susan Parkhurst for helpful discussions and encouragement; and Debbie Chapman, Susan Parkhurst, and our laboratory colleagues for critical comments on the manuscript.

This work was supported by grant HD24875 to P.S.