Velvet, a Dominant Egfr Mutation that Causes Wavy Hair and Defective Eyelid Development in Mice

Xin Du, Koichi Tabeta, Kasper Hoebe, Haiquan Liu, Navjiwan Mann, Suzanne Mudd, Karine Crozat, Sosathya Sovath, Xiaohua Gong, Bruce Beutler

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

In the course of a large-scale program of ENU mutagenesis, we isolated a dominant mutation, called Velvet. The mutation was found to be uniformly lethal to homozygotes, which do not survive E13.5. Mice heterozygous for the Velvet mutation are born with eyelids open and demonstrate a wavy coat and curly vibrissae. The mutation was mapped to the proximal end of chromosome 11 by genome-wide linkage analysis. On 249 meioses, the locus was confined to a 2. 7-Mb region, which included the epidermal growth factor receptor gene (Egfr). An A → G transition in the Egfr coding region of Velvet mice was identified, causing the amino acid substitution D833G. This substitution alters an essential triad of amino acids (DFG → GFG) that is normally required for coordination of the ATP substrate. As such, kinase activity is at least mostly abolished, but quaternary structure of the receptor is presumably maintained, accounting for the dominant effect. Velvet is the first known dominant representative of the Egfr allelic series that is fully viable, a fact that makes it particularly useful for developmental studies.

Original languageEnglish (US)
Pages (from-to)331-340
Number of pages10
JournalGenetics
Volume166
Issue number1
DOIs
StatePublished - Jan 2004

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Velvet, a Dominant Egfr Mutation that Causes Wavy Hair and Defective Eyelid Development in Mice'. Together they form a unique fingerprint.

Cite this