A mutation in the epidermal growth factor receptor in waved-2 mice has a profound effect on receptor biochemistry that results in impaired lactation.

KJ Fowler, F Walker, W Alexander… - Proceedings of the …, 1995 - National Acad Sciences
KJ Fowler, F Walker, W Alexander, ML Hibbs, EC Nice, RM Bohmer, GB Mann, C Thumwood…
Proceedings of the National Academy of Sciences, 1995National Acad Sciences
The mutant mouse waved-2 (wa-2) is strikingly similar to transforming growth factor alpha-
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 …
The mutant mouse waved-2 (wa-2) is strikingly similar to transforming growth factor alpha-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.
National Acad Sciences