Miettinen P J, Berger J E, Meneses J, Phung Y, Pedersen R A, Werb Z, Derynck R
Department of Growth and Development, University of California, San Francisco 94143-0640, USA.
Nature. 1995 Jul 27;376(6538):337-41. doi: 10.1038/376337a0.
Since the discovery that epidermal growth factor (EGF) can accelerate opening of the eyelids, the EGF receptor (EGF-R) has been extensively studied and is now considered to be a prototype tyrosine kinase receptor. Binding of EGF or of transforming growth factor-alpha (TGF-alpha) or other related factors activates the receptor and induces cell proliferation and differentiation. Although it is not found on haematopoietic cells, the EGF-R is widely expressed in mammals and has been implicated in various stages of embryonic development. Here we investigate the developmental and physiological roles of this receptor and its ligands by inactivating the gene encoding EGF-R. We find that EGF-R-/- mice survive for up to 8 days after birth and suffer from impaired epithelial development in several organs, including skin, lung and gastrointestinal tract.
自从发现表皮生长因子(EGF)可加速眼睑睁开以来,表皮生长因子受体(EGF-R)已得到广泛研究,如今被视为酪氨酸激酶受体的原型。EGF、转化生长因子-α(TGF-α)或其他相关因子与之结合会激活该受体,并诱导细胞增殖和分化。尽管造血细胞上未发现EGF-R,但它在哺乳动物中广泛表达,并与胚胎发育的各个阶段有关。在此,我们通过使编码EGF-R的基因失活来研究该受体及其配体的发育和生理作用。我们发现,EGF-R基因敲除小鼠出生后能存活长达8天,并在包括皮肤、肺和胃肠道在内的多个器官中出现上皮发育受损的情况。