Regulated expression of alpha-fetoprotein genes in transgenic mice.
Regulated expression of alpha-fetoprotein genes in transgenic mice.
复制标题
转基因小鼠中甲胎蛋白基因的表达调节。
DOI：
10.1101/sqb.1985.050.01.047
复制
发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Tilghman,SM
中科院分区：
文献类型：
--
作者：
Krumlauf,R;Hammer,RE;Brinster,R;Chapman,VM;Tilghman,SM
真核生物已经进化出多种方式来产生细胞基因的组织特异性表达的变异。在某些情况下，基因复制和调控序列的分歧已被用来实现这一目标，最典型的例子是从海胆（Angerer 和 Davidson 1984）到人类（Gunning 等人 1983）的肌动蛋白基因家族。降钙素基因中单拷贝基因初级转录物的选择性剪接（Rosenfeld et al. 1984）和小鼠α-淀粉酶基因中重复启动子的组织特异性使用（Schibler et al. 1983）代表了单拷贝基因多样性的构建方式。这些机制都不能用来解释鼠甲胎蛋白（AFP）和白蛋白基因的多样化表达模式。这些基因是 5 亿年前基因复制的产物（Kioussis 等，1981），在小鼠 5 号染色体上形成一个小型多基因家族（D'Eustachio 等，1981；Ingrain 等，1981）。这两个基因在胚胎发育过程中在卵黄囊内脏内胚层、胎儿肝脏和胎儿胃肠道中同时激活（Tilghman 和 Belayew 1982；Young 和 Tilghman 1984）。然而，这些组织中 AFP 和白蛋白 mRNA 的水平明显不同，AFP mRNA 在内脏内胚层中占 mRNA 的 20%，在胎儿肝脏中占 10%，在肠道中占不到 0.1%（Andrews 等人，1982 年；Janzen 等人，1982 年；Tilghman 和 Belayew，1982 年）。另一方面，白蛋白 mRNA 仅在肝脏中以高水平存在。
Eukaryotic organisms have evolved multiple ways in which to generate variation in the tissue-specific expression of cellular genes. In some instances, gene duplication followed by divergence of the regulatory sequences has been used to accomplish this, as best typified by the actin gene families from sea urchins (Angerer and Davidson 1984) to humans (Gunning et al. 1983). Alternative splicing of the primary transcripts of a single-copy gene in the calcitonin gene (Rosenfeld et al. 1984) and tissue-specific use of duplicated promoters in the mouse a-amylase gene (Schibler et al. 1983) represent ways in which diversity is built into single-copy genes.None of these mechanisms can be invoked to explain the diverse pattern of expression of the murine a-fetoprotein (AFP) and albumin genes. These genes, which arose as the products of a gene duplication 500 million years ago (Kioussis et al. 1981), form a small multigene family on chromosome 5 of the mouse (D'Eustachio et al. 1981; Ingrain et al. 1981). Both genes are activated in concert during embryonic development in the visceral endoderm of the yolk sac, the fetal liver, and the fetal gastrointestinal tract (Tilghman and Belayew 1982; Young and Tilghman 1984). However the levels of AFP and albumin mRNA are markedly different in these tissues, with AFP mRNA constituting 20% of the mRNA in the visceral endoderm, 10% in fetal liver, and less than 0.1% o in the gut (Andrews et al. 1982; Janzen et al 1982; Tilghman and Belayew 1982). Albumin mRNA, on the other hand, is present at high levels only in liver.