GENETIC ABLATION - TARGETED EXPRESSION OF A TOXIN GENE CAUSES MICROPHTHALMIA IN TRANSGENIC MICE
GENETIC ABLATION - TARGETED EXPRESSION OF A TOXIN GENE CAUSES MICROPHTHALMIA IN TRANSGENIC MICE
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DOI：
10.1126/science.3685993
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发表时间：
1987-12-11
期刊：
影响因子：
56.9
通讯作者：
BERNSTEIN, A
中科院分区：
文献类型：
--
作者：
BREITMAN, ML;CLAPOFF, S;BERNSTEIN, A
谱系特异性调控元件可用于指导转基因小鼠中多种基因在特定组织中的表达。如果杂合构建体含有编码细胞毒性基因产物的基因，则可以实现特定细胞谱系的遗传消融。我们通过将与白喉毒素A链基因的编码区融合的小鼠γ 2-晶状体蛋白启动子引入受精卵中，产生了6只转基因小鼠。其中三只小鼠和所有分析的转基因后代都是小眼的。这些小鼠的晶状体显示出相当大的异质性：一些在形态上几乎正常，但尺寸减小，而另一些则严重异常，核纤维细胞缺乏。这些研究表明，特定细胞类型的程序化消融可以通过生殖系稳定传播。
Lineage-specific regulatory elements can be used to direct expression of a variety of genes to specific tissues in transgenic mice. If the hybrid constructs contain a gene encoding a cytotoxic gene product, then genetic ablation of a specific cell lineage can be achieved. We have generated six transgenic mice by introducing into fertilized eggs the mouse .gamma.2-crystallin promoter fused to the coding region of the diphtheria toxin A-chain gene. Three of these mice and all the transgenic offspring analyzed were microphthalmic. The lenses of these mice displayed considerable heterogeneity: some were almost normal morphologically but reduced in size, whereas others were grossly aberrant and deficient in nuclear fiber cells. These studies indicate that programmed ablation of specific cell types can be stably transmitted through the germ line.