Velvet, a dominant Egfr mutation that causes wavy hair and defective eyelid development in mice
Velvet, a dominant Egfr mutation that causes wavy hair and defective eyelid development in mice
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DOI：
10.1534/genetics.166.1.331
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Beutler, B
中科院分区：
文献类型：
--
作者：
Du, X;Tabeta, K;Beutler, B
在ENU诱变的大规模计划的过程中，我们分离出一个显性突变，称为天鹅绒。发现该突变对纯合子是一致致死的，其不能在E13.5存活。天鹅绒突变的杂合子小鼠出生时眼睑张开，并表现出波浪状的皮毛和卷曲的触须。通过全基因组连锁分析将该突变定位于11号染色体的近端。在249个减数分裂中，该位点仅限于2.7 Mb区域，其中包括表皮生长因子受体基因（Egfr）。在天鹅绒小鼠的Egfr编码区中鉴定出A -> G转换，导致氨基酸取代D833 G。这种取代改变了ATP底物配位通常所需的必需氨基酸三联体（DFG -> GFG）。因此，激酶活性至少大部分被消除，但受体的四级结构可能被维持，这是主要作用的原因。Velvet是Egfr等位基因系列中第一个已知的完全可行的显性代表，这一事实使其对发育研究特别有用。
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.