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 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.
Fowler
K J
KJ
Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Victoria, Australia.
Walker
F
F
Alexander
W
W
Hibbs
M L
ML
Nice
E C
EC
Bohmer
R M
RM
Mann
G B
GB
Thumwood
C
C
Maglitto
R
R
Danks
J A
JA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000502:physiology*; D007774:Lactation; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D019000:Phosphotyrosine; D017354:Point Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D017931:DNA Primers; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases