MOLECULAR BIOLOGY OF THE APOA-II GENE

人apoA-II基因的整个核酸序列已被克隆。 测定 apoA-II基因的结构与其他基因相似， 载脂蛋白，如apoA-I、apoE和apoC-III。 apoA-II基因 如上述基因一样，由三个内含子和四个外显子组成。 的 内含子的位置在所有四个基因中相似。 启动子区域作为 以及一个可能的Z-DNA元件已经被确定。 的知识 基因的结构将允许更详细地研究表达。 为了更好地理解apoA-II的加工过程， 在人胸导管淋巴液和血浆以及培养物中分析 来自正常肝细胞和肝癌细胞系HepG2的培养基。 原载脂蛋白A-II 和apoA-II的几种亚型，包括唾液酸化形式， 鉴定 ProapoA-II具有6.79的显著碱性pI，这是由于 三个额外的带正电荷的残基， 载脂蛋白A-II 主要成熟同种型的pI为4.90。 唾液酸是 酸性更强，表观分子量稍高。 的 几种血脂异常的亚型模式不同于正常 控制 这种差异性的原因尚未完全了解。 apoB-100基因和mRNA已在正常受试者中进行了分析， 无β脂蛋白血症（ABL）患者。 apoB基因存在于ABL中， Southern杂交法确定与正常对照无结构差异 印迹分析 ABL中apoB-100 mRNA的大小与正常人相同 mRNA，但其浓度降低。 apoB的缺失， 然而，ABL患者的血浆不能用这种减少来解释。 我们 结论是ABL的缺陷是翻译后和额外的 目前正在进行研究，以确定缺陷的特征。

The entire nucleic acid sequence of the human apoA-II gene has been determined. The structure of the apoA-II gene is similar to that of other apolipoproteins, like apoA-I, apoE, and apoC-III. The apoA-II gene consists as the aforementioned genes of three introns and four exons. The position of the introns is similar in all four genes. Promoter regions as well as a possible Z-DNA element have been identified. The knowledge of the structure of the gene will allow to study the expression in more detail. To better understand the processing of apoA-II its isoforms have been analyzed in human thoracic duct lymph and plasma as well as in culture media from normal hepatocytes and the hepatoma cell line HepG2. ProapoA-II and several isoforms of apoA-II including sialylated forms were identified. ProapoA-II has a strikingly basic pI of 6.79 which is caused by three additional positively charged residues as compared to mature apoA-II. The major mature isoform has a pI of 4.90. The sialoforms are more acidic and have a slightly higher apparent molecular weight. The isoform pattern in several dyslipidemias is different from the normal control. The reason for this variability is not yet fully understood. The apoB-100 gene and mRNA have been analyzed in normal subjects and abetalipoproteinemic (ABL) patients. The apoB gene is present in ABL and not structurally different from normal controls as determined by Southern blot analysis. The apoB-100 mRNA in ABL is of the same size as the normal mRNA, but its concentration is reduced. The absence of apoB from the plasma of ABL-patients, however, cannot be explained by this reduction. We conclude that the defect in ABL is post-translational and additional studies to characterize the defect are being undertaken.