Fowler K J, Walker F, Alexander W, Hibbs M L, Nice E C, Bohmer R M, Mann G B, Thumwood C, Maglitto R, Danks J A
Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Victoria, Australia.
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1465-9. doi: 10.1073/pnas.92.5.1465.
The mutant mouse waved-2 (wa-2) is strikingly similar to transforming growth factor alpha-deficient mice generated by gene targeting in embryonic stem cells. We confirm that wa-2 is a point mutation (T-->G resulting in a valine-->glycine substitution at residue 743) in the gene encoding the epidermal growth factor (EGF) receptor. wa-2 fibroblastic cells lack high-affinity binding sites for EGF, and the rate of internalization of EGF is retarded. Although the tyrosine kinase activity of wa-2 EGF receptors is significantly impaired, NIH 3T3 cells lacking endogenous EGF receptors but overexpressing recombinant wa-2 EGF receptor cDNA are mitogenically responsive to EGF. While young and adult wa-2 mice are healthy and fertile, 35% of wa-2 mice born of homozygous wa-2 mothers die of malnutrition because of impaired maternal lactation.
突变小鼠waved-2（wa-2）与通过胚胎干细胞基因靶向产生的转化生长因子α缺陷小鼠极为相似。我们证实wa-2是编码表皮生长因子（EGF）受体的基因中的一个点突变（T→G，导致第743位残基的缬氨酸→甘氨酸替换）。wa-2成纤维细胞缺乏EGF的高亲和力结合位点，并且EGF的内化速率受到阻碍。尽管wa-2 EGF受体的酪氨酸激酶活性显著受损，但缺乏内源性EGF受体但过表达重组wa-2 EGF受体cDNA的NIH 3T3细胞对EGF有促有丝分裂反应。虽然幼年和成年wa-2小鼠健康且可育，但35%由纯合wa-2母亲所生的wa-2小鼠因母体泌乳受损而死于营养不良。
