title: Velvet, a dominant Egfr mutation that causes wavy hair and defective eyelid development in mice.
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.
authors.affiliation: Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.forename: Koichi
authors.initials: K
authors.lastname: Tabeta
authors.forename: Kasper
authors.initials: K
authors.lastname: Hoebe
authors.forename: Haiquan
authors.initials: H
authors.lastname: Liu
authors.forename: Navjiwan
authors.initials: N
authors.lastname: Mann
authors.forename: Suzanne
authors.initials: S
authors.lastname: Mudd
authors.forename: Karine
authors.initials: K
authors.lastname: Crozat
authors.forename: Sosathya
authors.initials: S
authors.lastname: Sovath
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Gong
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
mesh_terms: D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005143:Eyelids / Q000002:abnormalities*; D005260:Female; D005799:Genes, Dominant; D018773:Genes, erbB-1; D006197:Hair / Q000002:abnormalities*; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy
chemical_list: D018076:DNA, Complementary; D066246:ErbB Receptors