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

Kerry J. Fowler, Francesca Walker, Warren Alexander, Margaret L. Hibbs, Edouard C. Nice, Ralph M. Bohmer, G. Bruce Mann, Cassandra Thumwood, Rosemarie Maglitto, Janine A. Danks, Runjen Chetty, Antony W. Burgess, Ashley R. Dunn

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184 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1465-1469
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number5
DOIs
Publication statusPublished - 28 Feb 1995
Externally publishedYes

Keywords

  • epidermal growth factor receptor signaling
  • mutant mouse
  • postnatal mortality
  • wa-2 mice

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