TY - JOUR
T1 - Velvet, a Dominant Egfr Mutation that Causes Wavy Hair and Defective Eyelid Development in Mice
AU - Du, Xin
AU - Tabeta, Koichi
AU - Hoebe, Kasper
AU - Liu, Haiquan
AU - Mann, Navjiwan
AU - Mudd, Suzanne
AU - Crozat, Karine
AU - Sovath, Sosathya
AU - Gong, Xiaohua
AU - Beutler, Bruce
PY - 2004/1
Y1 - 2004/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=12144288188&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12144288188&partnerID=8YFLogxK
U2 - 10.1534/genetics.166.1.331
DO - 10.1534/genetics.166.1.331
M3 - Article
C2 - 15020428
AN - SCOPUS:12144288188
SN - 0016-6731
VL - 166
SP - 331
EP - 340
JO - Genetics
JF - Genetics
IS - 1
ER -