REGULATION OF ALPHA-FETOPROTEIN GENE EXPRESSION

α-胎蛋白基因表达的调节

• 批准号: 3482563
• 负责人: SHIRLEY M. TILGHMAN
• 金额: $ 39.6万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3482563
• 关键词: DNA; Escherichia coli; RNA splicing; affinity chromatography; alpha fetoprotein; bacteriophage lambda; basement membrane; cell growth regulation; chemical fingerprinting; clone cells; density gradient ultracentrifugation; developmental genetics; electron microscopy; embryo /fetus; embryo /fetus protein; gel electrophoresis; gene duplication; gene expression; genetic manipulation; genetic mapping; genetic recombination; genetic transcription; hamsters; hepatocellular carcinoma; hybrid cells; laboratory mouse; liver; liver cells; mature animal; messenger RNA; molecular cloning; neoplasm /cancer immunology; nucleic acid hybridization; nucleic acid sequence; protein biosynthesis; radiotracer; serum albumin; teratoma; tritium; vitelline membrane

The major protein component in the serum of the developing mammalian fetus is alpha-fetoprotein (AFP), which is synthesized in the embryonic liver and visceral endoderm of the yolk sac. After birth, the rate of synthesis of AFP in liver decreases drastically to levels that are barely detectable in nonpregnant adults. Synthesis of AFP is resumed in adult liver during liver regeneration and in specific tumors such as hepatomas and teratocarcinomas. In contrast, serum albumin, which is the major serum protein synthesized by the adult liver, increases from low levels early in development, to high, relatively constant levels after birth and in adult life. These serum proteins arose in evolution as the consequence of a gene duplication and are tightly linked in tandem on chromosome 5 in mice. Two transacting regulatory genes that affect AFP, but not albumin transcription in developing liver, have been described genetically. These genes recently have been shown to be pleiotrophic in that they affect transcription of other unlinked genes in addition to AFP. We are currently developing genetic and biochemical assays for the products of these regulatory genes that will allow us to isolate them and determine their mode of action. At the same time, the DNA sequences required for tissue-specific transcription of the AFP and albumin genes in vivo, using DNA-mediated gene transfer into both F9 teratocarcinoma cells and fertilized mouse eggs, are being identified. (M)

哺乳动物胎儿血清中的主要蛋白质成分 是甲胎蛋白（AFP），在胚胎肝脏中合成， 卵黄囊的内脏内胚层。 出生后， 肝脏中的AFP急剧下降到几乎检测不到的水平， 未怀孕的成年人 AFP的合成在成人肝脏中恢复， 肝再生和特定肿瘤如肝细胞瘤和 畸胎瘤 相反，血清白蛋白，这是主要的血清 由成人肝脏合成的蛋白质，从早期的低水平增加， 在出生后和成年后， 生活 这些血清蛋白是在进化过程中由一个基因 在小鼠的5号染色体上紧密连锁。 两 影响AFP但不影响白蛋白转录的反式调节基因 在肝脏发育过程中的作用。 这些基因最近 已被证明是多效性的，因为它们影响 除了AFP之外，还有其他非连锁基因。 我们目前正在开发 这些调控基因产物的遗传和生物化学分析 这样我们就能把它们分离出来并确定它们的行动模式 在 同时，组织特异性转录所需的DNA序列 的AFP和白蛋白基因在体内，使用DNA介导的基因转移到 F9畸胎癌细胞和受精的小鼠卵， 鉴定 （百万）