Chepelinsky A B, Khillan J S, Mahon K A, Overbeek P A, Westphal H, Piatigorsky J
Laboratory of Molecular and Developmental Biology, National Eye Institute, Bethesda, MD 20892.
Environ Health Perspect. 1987 Nov;75:17-24. doi: 10.1289/ehp.877517.
The abundant soluble proteins of the eye lens, the crystallins, are encoded by several gene families which are developmentally regulated in the embryonic lens. We have studied the expression of the murine alpha A-crystallin gene. Transfection experiments using the pSVO-CAT vector and explanted lens epithelia from embryonic chickens demonstrated proximal (-88 to -60) and distal (-111 to -85) regulatory sequences which interact when the alpha A-crystallin promoter is activated in the lens cells. Transgenic mouse experiments showed that the sequence between positions -366 to +46 of the alpha A-crystallin promoter can drive foreign genes selectively in the lens. A fusion gene consisting of this alpha A-crystallin promoter sequence and the T-antigen gene of SV40 produced a lens tumor in transgenic mice. Thus, crystallin promoters provide a useful model for tissue-specific gene expression and permit targeting the expression of foreign genes to a highly differentiated tissue during development.
眼晶状体丰富的可溶性蛋白质即晶状体蛋白,由几个基因家族编码,这些基因家族在胚胎晶状体发育过程中受到调控。我们研究了小鼠αA-晶状体蛋白基因的表达。使用pSVO-CAT载体和来自胚胎鸡的外植晶状体上皮进行的转染实验表明,当αA-晶状体蛋白启动子在晶状体细胞中被激活时,近端(-88至-60)和远端(-111至-85)调控序列会相互作用。转基因小鼠实验表明,αA-晶状体蛋白启动子-366至+46位之间的序列可在晶状体中选择性地驱动外源基因。由该αA-晶状体蛋白启动子序列和SV40的T抗原基因组成的融合基因在转基因小鼠中产生了晶状体肿瘤。因此,晶状体蛋白启动子为组织特异性基因表达提供了一个有用的模型,并允许在发育过程中将外源基因的表达靶向到高度分化的组织。