DEVELOPMENTAL REGULATION OF ALPHA-FETOPROTEIN GENES IN TRANSGENIC MICE
DEVELOPMENTAL REGULATION OF ALPHA-FETOPROTEIN GENES IN TRANSGENIC MICE
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DOI：
10.1128/mcb.5.7.1639
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发表时间：
1985-01-01
影响因子：
5.3
通讯作者：
BRINSTER, RL
中科院分区：
文献类型：
--
作者：
KRUMLAUF, R;HAMMER, RE;BRINSTER, RL
小鼠甲胎蛋白基因在胚胎发育过程中在胚外卵黄囊的内脏内胚层以及胎儿肝脏和肠道中被激活。该基因的转录随后在新生儿肝脏中受到抑制。为了询问组织特异性激活所需的DNA序列元件与出生后基因发育调节所需的DNA序列元件是否相同或不同，将甲胎蛋白基因的修饰拷贝显微注射到受精小鼠卵中。 对发育至足月并携带修饰基因的整合拷贝的那些动物进行表达分析。在.apprx中。在50%的此类动物中，引入的基因仅在表达真正的甲胎蛋白基因的3个细胞谱系中具有活性。它的表达在新生儿肝脏中受到抑制。修饰的基因包括 7 或 14 KB 对的 5'' 侧翼 DNA，包含指导组织特异性表达和发育调节的 DNA 序列信息。观察到 50% 携带修饰基因的小鼠不在任何组织中表达该基因，再加上表达水平在表达转基因动物之间存在很大差异的事实，表明该基因对其在小鼠基因组中的整合位点敏感。
The mouse .alpha.-fetoprotein gene is activated in embryonic development in the visceral endoderm of the extraembryonic yolk sac and the fetal liver and gut. Transcription of the gene is subsequently repressed in the neonatal liver. To ask whether the DNA sequence elements required for tissue-specific activation are the same or different from those required for postnatal developmental regulation of the gene, modified copies of the .alpha.-fetoprotein gene were microinjected into fertilized mouse eggs. Those animals which developed to term and carried integrated copies of the modified gene were analyzed for expression. In .apprx. 50% of such animals, the introduced gene was active only in the 3 cell lineages which expressed the authentic .alpha.-fetoprotein gene. Its expression was repressed in the neonatal liver. The modified genes, which included either 7 or 14 kilobase pairs of 5''-flanking DNA, contained the DNA sequence information to direct both tissue-specific expression and developmental regulation. The observation that 50% of the mice which carried the modified gene did not express it in any tissue, combined with the fact that the level of expression was highly variable between expressing transgenic animals, suggested that the gene was susceptible to its site of integration in the mouse genome.