A MUTATION IN THE EPIDERMAL GROWTH-FACTOR RECEPTOR IN WAVED-2 MICE HAS A PROFOUND EFFECT ON RECEPTOR BIOCHEMISTRY THAT RESULTS IN IMPAIRED LACTATION

The mutant mouse waved-2 (wa-2) is strikingly similar to transforming growth factor alpha-deficient mice generated by gene targeting in embr yonic stem cells. We confirm that wa-2 is a point mutation (T --> G re sulting in a valine --> glycine substitution at residue 743) in the ge ne encoding the epidermal growth factor (EGF) receptor. wa-2 fibroblas tic cells lack high-affinity binding sites for EGF, and the rate of in ternalization of EGF is retarded. Although the tyrosine kinase activit y of wa-2 EGF receptors is significantly impaired, NIH 3T3 cells lacki ng endogenous EGF receptors but overexpressing recombinant wa-2 EGF re ceptor cDNA are mitogenically responsive to EGF. While young and adult wa-2 mice are healthy and fertile, 35% of wa-2 mice born of homozygou s wa-2 mothers die of malnutrition because of impaired maternal lactat ion.