Wa5 is a novel ENU-induced antimorphic allele of the epidermal growth factor receptor

Wa5 is a novel ENU-induced antimorphic allele of the epidermal growth factor receptor Mice heterozygous for the N-ethyl-N-nitrosourea-induced Waved-5 (Wa5) mutation, isolated in a screen for dominant, visible mutations, exhibit a wavy coat similar to mice homozygous for the recessive Tgfa wa1 or Egfr wa2 alleles. In this study, we show that Wa5 is a new allele of Egfr (Egfr Wa5 ) containing a missense mutation within the coding region for the highly conserved DFG motif of the tyrosine kinase domain. In vivo analysis of placental development, modification of Apc Min tumorigenesis, and levels of EGF-dependent EGFR phosphorylation demonstrates that Egfr Wa5 functions as an antimorphic allele, recapitulating many abnormalities associated with reduced EGFR activity. Furthermore, Egfr wa5 enhances Egfr Wa2 compound or Tgfa tm1Dcl double mutants exposing additional EGFR-dependent phenotypes. In vitro characterization shows that the antimorphic property of Egfr Wa5 is caused by a kinase-dead receptor acting as a dominant negative. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

Wa5 is a novel ENU-induced antimorphic allele of the epidermal growth factor receptor

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Publisher
Springer-Verlag
Copyright
Copyright © 2004 by Springer-Verlag
Subject
Philosophy
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s00335-004-2384-2
Publisher site
See Article on Publisher Site

Abstract

Mice heterozygous for the N-ethyl-N-nitrosourea-induced Waved-5 (Wa5) mutation, isolated in a screen for dominant, visible mutations, exhibit a wavy coat similar to mice homozygous for the recessive Tgfa wa1 or Egfr wa2 alleles. In this study, we show that Wa5 is a new allele of Egfr (Egfr Wa5 ) containing a missense mutation within the coding region for the highly conserved DFG motif of the tyrosine kinase domain. In vivo analysis of placental development, modification of Apc Min tumorigenesis, and levels of EGF-dependent EGFR phosphorylation demonstrates that Egfr Wa5 functions as an antimorphic allele, recapitulating many abnormalities associated with reduced EGFR activity. Furthermore, Egfr wa5 enhances Egfr Wa2 compound or Tgfa tm1Dcl double mutants exposing additional EGFR-dependent phenotypes. In vitro characterization shows that the antimorphic property of Egfr Wa5 is caused by a kinase-dead receptor acting as a dominant negative.

Journal

Mammalian GenomeSpringer Journals

Published: Jan 1, 2004

References

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