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Abstract
Activation of the epidermal growth factor receptor (EGFR) family is thought to play a critical role in both embryogenesis and oncogenesis. The diverse biological activities of the EGFR family are achieved through various ligand-receptor and receptor-receptor interactions. One receptor that has been found to play a central role in this signaling network is ErbB-2/Neu, and it is considered the preferred heterodimerization partner for other members of the EGFR family. To assess the importance of the catalytic activity of ErbB-2 in embryonic development, we have generated mice expressing a kinase-dead erbB-2 cDNA under the transcriptional control of the endogenous promoter. Here, we show that mice homozygous for the kinase-dead erbB-2 allele die at midgestation and display the same spectrum of embryonic defects seen in erbB-2 knockout mutants. These observations suggest that the catalytic activity of ErbB-2 is essential for normal embryonic development.
R.C. and W.R.H contributed equally to this work.
We thank Margaret Hibbs and Ashley Dunn for providing genomic clones and Michael Rudnicki and Christo Goridis for providing plasmids used in this study. We also thank Brian Allore and Dinsdale Gooden at the MOBIX Central Facility, McMaster University, for automated DNA sequencing analysis and oligonucleotide synthesis.
This work was supported by a grant awarded to W.J.M. by the Medical Research Council of Canada. W.J.M. is a recipient of a Medical Research Council of Canada scientist award, and R.C. was supported by a studentship from the Cancer Research Society of Canada and a U.S. Army D.O.D. studentship.