The mutant mouse waved-2 (wa-2) is strikingly similar to transforming growth factor α-deficient mice generated by gene targeting in embryonic stem cells. We confirm that wa-2 is a point mutation (T → G resulting in a valine → glycine substitution at residue 743) in the gene encoding the epidermal growth factor (EGF) receptor. wa-2 fibroblastic cells lack high-affinity binding sites for EGF, and the rate of internalization of EGF is retarded. Although the tyrosine kinase activity of wa-2 EGF receptors is significantly impaired, NIH 3T3 cells lacking endogenous EGF receptors but overexpressing recombinant wa-2 EGF receptor cDNA are mitogenically responsive to EGF. While young and adult wa-2 mice are healthy and fertile, 35% of wa-2 mice born of homozygous wa-2 mothers die of malnutrition because of impaired maternal lactation.
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 28 Feb 1995|
- epidermal growth factor receptor signaling
- mutant mouse
- postnatal mortality
- wa-2 mice