共查询到20条相似文献,搜索用时 0 毫秒
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胎儿血红蛋白是胎儿体内主要的血红蛋白类型,是由两条α肽链和两条γ肽链组成的四聚体。出生后胎儿血红蛋白在人体中的表达急剧降低至1%,由两条α肽链和两条β肽链组成的成人血红蛋白取而代之成为主要的血红蛋白类型。β地中海贫血和镰刀型细胞贫血发病原因均基于β-珠蛋白基因发生突变,致使β-珠蛋白合成不足或异常,进而引起一系列临床症状。诸多实验结果及临床疗效表明,提高患者体内γ-珠蛋白的表达可部分替代异常β-珠蛋白从而有效缓解患者的临床症状。随着基因治疗的发展,如何安全高效的再激活胎儿血红蛋白的表达成为治疗β型地中海贫血和镰刀型细胞贫血患者的重要科学命题。本文重点回顾近年来γ-珠蛋白表达的调控机制,以期对寻找更加有效激活胎儿血红蛋白的方法提供参考。 相似文献
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Grewal SI 《Journal of cellular physiology》2000,184(3):311-318
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Yong Shen Rick Li Kristian Teichert Kara E. Montbleau Jeffrey M. Verboon Richard A. Voit Vijay G. Sankaran 《PLoS genetics》2021,17(10)
Increased production of fetal hemoglobin (HbF) can ameliorate the severity of sickle cell disease and β-thalassemia. BCL11A has been identified as a key regulator of HbF silencing, although its precise mechanisms of action remain incompletely understood. Recent studies have identified pathogenic mutations that cause heterozygous loss-of-function of BCL11A and result in a distinct neurodevelopmental disorder that is characterized by persistent HbF expression. While the majority of cases have deletions or null mutations causing haploinsufficiency of BCL11A, several missense variants have also been identified. Here, we perform functional studies on these variants to uncover specific liabilities for BCL11A’s function in HbF silencing. We find several mutations in an N-terminal C2HC zinc finger that increase proteasomal degradation of BCL11A. We also identify a distinct C-terminal missense variant in the fifth zinc finger domain that we demonstrate causes loss-of-function through disruption of DNA binding. Our analysis of missense variants causing loss-of-function in vivo illuminates mechanisms by which BCL11A silences HbF and also suggests potential therapeutic avenues for HbF induction to treat sickle cell disease and β-thalassemia. 相似文献
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Transcriptional transgene silencing and chromatin components 总被引:19,自引:0,他引:19
Meyer P 《Plant molecular biology》2000,43(2-3):221-234
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D Shore 《Current biology : CB》2001,11(20):R816-R819
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J Müller 《The EMBO journal》1995,14(6):1209-1220
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Using isoelectric focusing, a fetal hemoglobin was found in the peripheral blood of C57BL/6 fetal mouse during the 14 to 20 days gestational period. In acid-urea polyacrylamide gel the pattern of this fetal hemoglobin was different from that of the adult hemoglobin. The mouse fetal hemoglobin was differentiated from the mouse adult hemoglobin by immunodiffusion reaction. It suggests that there is a transient fetal hemoglobin in the C57BL/6 mouse during gestational age. 相似文献
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R M Zucker 《Biochimica et biophysica acta》1982,703(2):212-215
A "fetal hemoglobin' has been reported to exist during mouse gestation, Investigations using CMC chromatography, starch gel electrophoresis or isoelectric focusing have shown a hemoglobin band from fetal tissues, and blood was obtained which was different from the adult hemoglobin and designated a "fetal hemoglobin'. In the current study isoelectric focusing was used to study the hemoglobins existing in the tissues and blood during fetal and neonatal development and the results suggest there is no "fetal hemoglobin' present during gestation. It appears that the hemoglobin designated as "fetal' in our laboratory was a methemoglobin formed by an incomplete reaction of KCN with the hemoglobin. The additional hemoglobin bands which were obtained from fetal liver or neonatal spleen tissues appeared to be a modified adult hemoglobin. 相似文献