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. 1995 Feb 28;92(5):1465–1469. doi: 10.1073/pnas.92.5.1465

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

K J Fowler 1, F Walker 1, W Alexander 1, M L Hibbs 1, E C Nice 1, R M Bohmer 1, G B Mann 1, C Thumwood 1, R Maglitto 1, J A Danks 1, et al.
PMCID: PMC42540  PMID: 7533293

Abstract

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.

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Selected References

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