A Murine Homologue of the Drosophila brainiac Gene Shows Homology to Glycosyltransferases and Is Required for Preimplantation Development of the Mouse

Abstract

The neurogenic gene brainiac was first isolated in Drosophila melanogaster, where it interacts genetically with members of the Notch signaling cascade. We have isolated a murine homologue of the Drosophila brainiac gene and delineated its highly specific expression pattern during development and adult life. We find particularly strong expression in the developing central nervous system, in the developing retina, and in the adult hippocampus. Targeted deletion of mouse Brainiac 1 expression leads to embryonic lethality prior to implantation. Null embryos can be recovered as blastocysts but do not appear to implant, indicating that mouse Brainiac 1, likely a glycosyltransferase, is crucial for very early development of the mouse embryo.

ACKNOWLEDGMENTS

We thank Oliver Smithies for the targeting vector pOSdupdel. In addition, we thank Ann Harrington for performing the blastocyst injections and for expert technical assistance with all mouse procedures, Monteserrat Michelmann for help with targeting ES cells and tissue culture procedures, Jan Pinkas and Nick Chester for helpful comments on the manuscript, and Katy Mclntyre for editing. We also thank all members of the Leder lab and the Harvard Medical School Department of Genetics for helpful comments and suggestions throughout the project.