Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.
Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.
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人类凝血因子 IX 基因发育调节的结构和功能基础：因子 IX Leyden。
DOI：
10.1073/pnas.87.12.4421
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发表时间：
1990
影响因子：
11.1
通讯作者：
Kurachi,K
中科院分区：
文献类型：
--
作者：
Hirosawa,S;Fahner,JB;Salier,JP;Wu,CT;Lovrien,EW;Kurachi,K
血友病B Leyden的特征是受影响个体中因子IX合成的异常发育调节。一个家族患有血友病B Leyden表型，发现在因子IX基因的核苷酸-6处有一个特定的单碱基突变（G-A）。突变位点位于5 '端非翻译序列的一个小区域，称为Leyden特异性区域（LS区域）。这个区域，大约40个碱基对的长度，包含了所有已知的因子IX莱顿基因（五个家庭）分析的唯一突变位点。这一事实有力地表明，LS区直接或间接参与因子IX生物合成的发育调节。如在培养的细胞（HepG 2）表达系统中所评估的，在核苷酸-20处以及在核苷酸-6处的碱基变化以及LS区域的3'半的缺失将因子IX基因的表达活性降低至正常对照的约15-31%。LS区结合至少两种蛋白质。雄激素以浓度依赖性方式显著增加突变型和正常型因子IX基因的转录活性。
Hemophilia B Leyden is characterized by unusual developmental regulation of factor IX synthesis in affected individuals. One family affected with the hemophilia B Leyden phenotype was found to have a specific single-base mutation (G----A) at nucleotide -6 of the factor IX gene. The mutation site was found in a small region of the 5'-untranslated sequence designated the Leyden-specific region (LS region). This region, approximately 40 base pairs in length, contains the unique mutation sites of all the known factor IX Leyden genes (five families) analyzed to date. This fact strongly suggests that the LS region is directly or indirectly involved in the developmental regulation of factor IX biosynthesis. Base changes at nucleotide -20 as well as at nucleotide -6 and deletions of the 3' half of the LS region reduced expression activity of the factor IX gene to approximately 15-31% that of the normal control, as assessed in a cultured cell (HepG2) expression system. The LS region binds at least two proteins. Androgen significantly increased the transcriptional activities of both mutant and normal factor IX genes in a concentration-dependent manner.