Feldman B, Poueymirou W, Papaioannou V E, DeChiara T M, Goldfarb M
Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Science. 1995 Jan 13;267(5195):246-9. doi: 10.1126/science.7809630.
Fibroblast growth factors (FGFs) are thought to influence many processes in vertebrate development because of their diverse sites of expression and wide range of biological activities in in vitro culture systems. As a means of elucidating embryonic functions of FGF-4, gene targeting was used to generate mice harboring a disrupted Fgf4 gene. Embryos homozygous for the null allele underwent uterine implantation and induced uterine decidualization but did not develop substantially thereafter. As was consistent with their behavior in vivo, Fgf4 null embryos cultured in vitro displayed severely impaired proliferation of the inner cell mass, whereas growth and differentiation of the inner cell mass were rescued when null embryos were cultured in the presence of FGF-4 protein.
成纤维细胞生长因子(FGFs)被认为会影响脊椎动物发育中的许多过程,这是因为它们在体外培养系统中具有多样的表达位点和广泛的生物学活性。作为阐明FGF-4胚胎功能的一种手段,基因打靶技术被用于产生携带Fgf4基因破坏的小鼠。纯合无效等位基因的胚胎能够进行子宫着床并诱导子宫蜕膜化,但此后基本不再发育。与它们在体内的表现一致,体外培养的Fgf4无效胚胎显示出内细胞团的增殖严重受损,而当在FGF-4蛋白存在的情况下培养无效胚胎时,内细胞团的生长和分化得到挽救。