MODULATION OF APOLIPOPROTEIN B GENE EXPRESSION

载脂蛋白B是乳糜粒上的主要载脂蛋白 密度脂蛋白、中间脂蛋白和低密度脂蛋白 脂蛋白。载脂蛋白B以两种形式存在于人血浆中，即 全长apoB-100和较短的apoB-48。合成了载脂蛋白B-100 主要由肝脏产生，而apoB-48则完全来源于 小肠。两种形式的蛋白质都是正常的 饮食和内源性脂质的转运和递送到靶点 纸巾。这两种蛋白质都是单一基因的产物，该基因编码一种 可以直接翻译成全长apoB-100的mRNA 或者，可替代地，通过转化单核苷酸来修饰 结果2153位密码子CAA被替换为 过早终止密码子UAA。这一修改导致了更短的 翻译产物apoB-48被称为信使核糖核酸“编辑”。通过 人和大鼠不同时期组织来源的mRNA分析 发展，我们的实验室今年已经证明了 编辑apoB mRNA在a组织中受发育控制，并且 物种特有的方式。此外，我们已经证明了其中一个 必需的发育组织特异性信号是甲状腺激素： 在没有甲状腺激素的情况下，正常的编辑不会在 肝脏，而小肠正常编辑；给药 甲状腺激素可以恢复发育中的肝脏的正常编辑。

Apolipoprotein B is the principal apolipoprotein on chylomicrons, ow density lipoproteins, intermediate lipoproteins, and low density lipoproteins. Apolipoprotein B exists in human plasma in two forms, the full length apoB-100 and the shorter apoB-48. ApoB-100 is synthesized primarily by the liver, whereas apoB-48 is derived exclusively from the small intestine. Both forms of the protein are requisite for the normal transport and delivery of dietary and endogenous lipids to target tissues. Both proteins are the product of a single gene which encodes a mRNA that may either be directly translated into the full-length apoB-100 or, alternatively, be modified by conversion of single nucleotide that results in the replacement of the codon CAA at position 2153 with the premature STOP codon UAA. This modification results in the shorter translation product apoB-48 and is referred to as mRNA "editing." By analysis of mRNA derived from human and rat tissues at various stages of development, our laboratory this year has demonstrated that the capacity to edit apoB mRNA is developmentally controlled in a -tissue and species-specific manner. Furthermore, we have demonstrated that one of the requisite developmental tissue-specific signals is thyroid hormone: in the absence of thyroid hormone normal editing does not develop in the liver, while the small intestine edits normally; administration of thyroid hormone can restore normal editing in the developing liver.