BUTYRATE INFUSIONS IN THE OVINE FETUS DELAY THE BIOLOGIC CLOCK FOR GLOBIN GENE SWITCHING
BUTYRATE INFUSIONS IN THE OVINE FETUS DELAY THE BIOLOGIC CLOCK FOR GLOBIN GENE SWITCHING
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DOI：
10.1073/pnas.85.22.8540
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发表时间：
1988-11-01
影响因子：
11.1
通讯作者：
KAN, YW
中科院分区：
文献类型：
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作者：
PERRINE, SP;RUDOLPH, A;KAN, YW
在许多哺乳动物物种中，从胎儿到成人血红蛋白表达的转换受发育时钟样机制的调节，并由胎儿的胎龄决定。延长胎儿珠蛋白基因的表达对于治疗由β异常引起的疾病具有重要的意义。球蛋白基因。在珠蛋白基因转换延迟的糖尿病母亲的婴儿中，丁酸的血浆浓度升高，在正常的珠蛋白基因转换期间，将丁酸注入子宫内插管的死亡羔羊。与对照组相比，四个丁酸酯治疗的胎儿中有三个的珠蛋白基因开关明显延迟，而在珠蛋白开关开始之前开始输注的一个胎儿中，珠蛋白基因开关完全被阻止。这些数据为研究和阻止血红蛋白转换的生物钟提供了一个模型。
The switch from fetal to adult hemoglobin expression is regulated in many mammalian species by a developmental clock-like mechanism and determined by the gestational age of the fetus. Prolonging fetal globin gene expression is of considerable interest for therapeutic potential in diseases caused by abnormal .beta.-globin genes. Butyric acid, which is found in increased plasma concentrations in infants of diabetic mothers who have delayed globin gene switching, was infused into catheterized fatal lambs in utero during the time of the normal globin gene switch period. The globin gene switch was significantly delayed in three of four butyrate-treated fetuses compared with controls and was entirely prevented in one fetus in whom the infusion was begun before the globin switch was under way. These data provide a model for investigating and arresting the biologic clock of hemoglobin switching.