Chow R L, Roux G D, Roghani M, Palmer M A, Rifkin D B, Moscatelli D A, Lang R A
Skirball Institute for Biomolecular Medicine, New York University Medical Center, NY 10016, USA.
Development. 1995 Dec;121(12):4383-93. doi: 10.1242/dev.121.12.4383.
To determine whether fibroblast growth factor (FGF) has a role in lens development, we have generated transgenic mice expressing a dominant-negative form of the murine FGF receptor-1 (FGFRDN) in the lens. Using the fibre cell-specific alpha A-crystallin promoter to express the FGFRDN, we have asked whether FGF is required for fibre cell differentiation. The transgenic mice display diminished differentiation of fibre cells as indicated by their reduced elongation. In addition, transgenic lenses have an unusual refractile anomaly that morphological and biochemical data show results from the apoptosis of fibre cells in the central region of the lens. These results show that lens fibre cells are dependent on FGF for their survival and differentiation, and demonstrate that growth factor deprivation in vivo can lead to apoptosis.
为了确定成纤维细胞生长因子(FGF)在晶状体发育中是否起作用,我们构建了在晶状体中表达小鼠FGF受体-1显性负性形式(FGFRDN)的转基因小鼠。利用纤维细胞特异性αA-晶状体蛋白启动子来表达FGFRDN,我们探究了FGF是否是纤维细胞分化所必需的。转基因小鼠表现出纤维细胞分化减弱,这表现为纤维细胞伸长减少。此外,转基因晶状体有一个异常的折射异常,形态学和生化数据表明这是由晶状体中央区域纤维细胞的凋亡导致的。这些结果表明晶状体纤维细胞的存活和分化依赖于FGF,并证明体内生长因子缺乏可导致细胞凋亡。