Regulation of human pyruvate kinase gene in red cells
红细胞中人丙酮酸激酶基因的调控
基本信息
- 批准号:09670165
- 负责人:
- 金额:$ 2.3万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:1997
- 资助国家:日本
- 起止时间:1997 至 1998
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
To identify regulatory gene sequence(s) responsible for the erythroid-specific expression of human erythroid-type pyruvate kinase (R-PK), we prepared two human PK mini-gene constructs and established 19 lines of transgenic mice.Although we have shown that the human R-PK promoter containing 4 GATA and 2 CACCC motifs had prominent transcription activity in both K562 and MEL cells, the promoter was not sufficient for in vivo transcription in the PK transgenic mice.We identified two DNaseI hypersensitive sites (HS) upstream of the human PK LR-gene, and an addition of the proximal HS (HS-I) enabled the linked PK transgene to express in an erythroid-specific manner, suggesting that the HS-I is an erythroid-specific enhancer of the human PK LR-gene.The HS-I contained one GATA, one CACCC and one purine rich motif (AGGGAGAAG), and the organization was similar to the erythroid-specific enhancer which had been identified in rat PK LR-gene.We have established three PK transgenic mice lines which overexpress human R-PK in red cells.The mu' LCR, the regulatory sequence of human beta-like globin locus was linked to the R-PK promoter and coding sequences, and used for microinjection.Red cell PK activities of the PK transgenic mice were about 2-3 fold of normal controls (83-122 IU/gHb, normal range 41.6*5.8), and human R-PK activities were demonstrated in the PK zymograms.Since the mu' LCR did not confer the position-independent, copy number-dependent expression of the PK transgene, the LCR might be influenced by position effect, and functioned as an erythroid-specific enhancer.
为了鉴定人红系特异性表达人红细胞型丙酮酸激酶(R-PK)的调控基因序列(S),我们制备了两个人PK微型基因构建体,建立了19个转基因小鼠系。虽然含有4个GATA基序和2个CACCC基序的人R-PK启动子在K562和MEL细胞中都具有显著的转录活性,但在PK转基因小鼠中,启动子不足以在体内转录。我们鉴定了人PK LR-基因上游的两个DNaseI高敏感位点(HS)。Hs-I是人PK受体基因的红系特异性增强子。HS-I含有一个GATA、一个CACCC和一个富嘌呤基序(AGGGAAG),其组织结构与已在大鼠PK LR基因中发现的红系特异性增强子相似。我们建立了三个在红细胞中高表达人R-PK的PK转基因小鼠。人β样珠蛋白基因的调控序列Mu‘LCR与R-PK启动子和编码序列相连,PK转基因小鼠的红细胞PK活性约为正常对照小鼠的2-3倍(83-122IU/gHb,正常范围41.6*5.8),并且在PK酶谱中证实了人的R-PK活性。由于Mu‘LCR不提供PK转基因基因的位置依赖、拷贝数依赖的表达,LCR可能受位置效应的影响,并作为红系特异性增强子发挥作用。
项目成果
期刊论文数量(20)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Tsujino K, Kano H, Hashimoto K, Fujii H, Jippo T, Morii E, Lee Y-M, Asai H, Miwa S, Kitamura Y.: "Delayed onset of hemolytic anemia in CBA-Pk-1^<slc>/Pk-1^<slc> mice with a point mutation of the gene encoding red blood cell type pyruvate kinase" Blood. 91
Tsujino K、Kano H、Hashimoto K、Fujii H、Jippo T、Morii E、Lee Y-M、Asai H、Miwa S、Kitamura Y.:“CBA-Pk-1^<slc>/Pk- 中溶血性贫血延迟发作
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- 影响因子:0
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- 通讯作者:
Hitoshi Kanno: "Expression and enzymatic characterization of human qlucose phosphate isomerase (GPI) variants accounting for GPI deficiency" Blood Cells Mol Dis. 24. 54-61 (1998)
Hitoshi Kanno:“导致 GPI 缺陷的人葡萄糖磷酸异构酶 (GPI) 变体的表达和酶学特征”Blood Cells Mol Dis。
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- 影响因子:0
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Yoshiaki Kajiyama: "p53 gene mutation in 150 dissected lymph nodes in a patient with esophageal cancer" Dis Esophagus. 11. 279-283 (1998)
Yoshiaki Kajiyama:“食管癌患者 150 个解剖淋巴结中的 p53 基因突变”Dis Esophagus。
- DOI:
- 发表时间:
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- 影响因子:0
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- 通讯作者:
Hitoshi Kanno: "Expression and enzymatic characterization of human glucose phosphate isomerase(GPI)variants accounting for GPI deficiency" Blood Cells Mol Dis. 24. 54-61 (1998)
Hitoshi Kanno:“导致 GPI 缺乏的人葡萄糖磷酸异构酶 (GPI) 变体的表达和酶学特征”Blood Cells Mol Dis。
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- 发表时间:
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- 影响因子:0
- 作者:
- 通讯作者:
Murakami K, Kanno H, Miwa S, Piomelli S.: "Human HK_R isozyme : the organization of the hexokinase-I gene, the erythroid-specific promoter and transcription initiation site." Mol Genet Metab. (in press). (1999)
Murakami K、Kanno H、Miwa S、Piomelli S.:“人类 HK_R 同工酶:己糖激酶-I 基因、红细胞特异性启动子和转录起始位点的组织。”
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- 影响因子:0
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KANNO Hitoshi其他文献
Traditional Craftwork and Rural Community : A case study on the Choma textile production in Japan.
传统手工艺和农村社区:日本 Choma 纺织品生产的案例研究。
- DOI:
- 发表时间:
2006 - 期刊:
- 影响因子:0
- 作者:
KATO Masayoshi;KANNO Hitoshi - 通讯作者:
KANNO Hitoshi
集団就職世代のライフヒストリ--成功者たちの回想を中心にして
集体就业一代的人生史--聚焦成功人士的回忆
- DOI:
- 发表时间:
2005 - 期刊:
- 影响因子:0
- 作者:
KATO Masayoshi;KANNO Hitoshi;黒田 英一 - 通讯作者:
黒田 英一
Ex-Vivo Expanded NK Cell Therapy Combined with Elotuzumab for MRD after Autologous Stem Cell Transplantation: A Phase I/ II Clinical Trial in Progress.
体外扩展 NK 细胞疗法联合 Elotuzumab 用于自体干细胞移植后 MRD:正在进行的 I/II 期临床试验。
- DOI:
- 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
HAGIWARA Shotaro;WANG Yan-Hua;KOBAYASHI Hirohito;KATO Yutaka;TANAKA Norina;IIZUKA Yuki;WATANABE Aya;ISHIYAMA Midori;SHINOHARA Akihito;KAZAMA Hiroshi;YOSHINAGA Kentaro;SHISEKI Masayuki;KANNO Hitoshi;TANAKA Junji - 通讯作者:
TANAKA Junji
KANNO Hitoshi的其他文献
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{{ truncateString('KANNO Hitoshi', 18)}}的其他基金
Andic properties and those spatial variability of Fulvic Andosols-related soils in certain hilly areas of northeastern Japan
日本东北部某些丘陵地区与黄腐安土相关的土壤的安第斯特性和空间变异
- 批准号:
23580085 - 财政年份:2011
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of novel gene therapy for congenital blood disorders using induced pluripotent stem cells
利用诱导多能干细胞开发治疗先天性血液疾病的新型基因疗法
- 批准号:
22591071 - 财政年份:2010
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
MOLECULAR MECHANISMS OF ACCELERATED ERYTHROID APOPTOSIS DUE TO A GLYCOLYTIC ENZYME DEFECT
糖酵解酶缺陷加速红细胞凋亡的分子机制
- 批准号:
14570131 - 财政年份:2002
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Physiological significance of pyruvate kinase isozymes in erythrocyte.
红细胞中丙酮酸激酶同工酶的生理意义。
- 批准号:
11670153 - 财政年份:1999
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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