Analysis of aromatase/estrogen system in the age-related diseases by developmental engineering techniques

利用发育工程技术分析年龄相关疾病中的芳香酶/雌激素系统

基本信息

  • 批准号:
    11470228
  • 负责人:
  • 金额:
    $ 8.9万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    1999
  • 资助国家:
    日本
  • 起止时间:
    1999 至 2001
  • 项目状态:
    已结题

项目摘要

Aromatase knockout (ArKO) mouse which exhibits complete loss of capacity for estrogen biosynthesis was prepared and examined for sexual differentiation of the brain. The results indicated obvious abnormalities in the sexual motivation, sexual behaviors, aggressiveness, and parental behaviors of ArKO mice. Aromatae in the mouse brain shows a transient peak of expression at the perinatal period critaical for sexual differentiation of the brain, and is localized in nerve cells of the specific brain regions, namely of the reproductive center of hypothalamus, preoptic area, and amygdala. To elucidate the regulatory mechanism of neuron-specific, region-specific, and developmental stage-specific expression of brain aromatase, a hybrid gene cosisting of the brain-specific promoter region of aromatase gene and a beta-galactosidase structural gene was introduced into a mouse oocyte to create a transgenic (TG) mouse, and expression of beta-galactosidase in the brain of the TG mouse was analyzed. … More Conseqeuntly, at least 6.4 kb promoter region upstream from the brain-specific exon 1 of mouse aromatase gene is essential for neuron-specific, region-specific, and developmental stage-specific expression of brain aromatase.Human aromatase gene is tissue-specifically regulated by alternative use of multiple exons 1 and promoters. To elucidate the regulatory mechanism of tissue-specific expression, a humanized TG mouse carrying a reporter gene (beta-galactosidase) controlled by the multiple promoters of human aromatase gene was prepared. In this TG mouse the reporter gene was expressed in ovarian granulosa cells, testis Leydig cells, placenta, fetus liver, skin bone' artery, adipose tissue. The distribution of expression of the reporter gene in the TG mouse was exactly the same as that of the aromatase gene in human. Furthermore, the tissue-preference of alternative exons 1a, 1b, 1c, and 1d in the tissues of the TG mouse was also the same as that of human. These results indicate that this humanized TG mouse is a useful model animal for analysis of tissue-specific expression of human aromatae gene. Less
制备表现出雌激素生物合成能力完全丧失的芳香化酶敲除(ArKO)小鼠,并检查脑的性别分化。结果表明,ArKO小鼠的性动机、性行为、攻击性和父母行为均出现明显异常。小鼠脑中的芳香素在围产期表现出短暂的表达高峰,这是大脑性别分化的关键时期,并且定位于特定脑区域的神经细胞,即下丘脑、视前区和杏仁核的生殖中心。为了阐明脑芳香化酶的神经元特异性、区域特异性和发育阶段特异性表达的调控机制,将芳香化酶基因的脑特异性启动子区和β-半乳糖苷酶结构基因组成的杂合基因导入小鼠卵母细胞,建立转基因(TG)小鼠,并分析TG小鼠脑中β-半乳糖苷酶的表达。 ...更多信息 因此,小鼠芳香酶基因脑特异性外显子1上游至少6.4kb的启动子区域对于脑芳香酶的神经元特异性、区域特异性和发育阶段特异性表达至关重要,人类芳香酶基因通过多个外显子1和启动子的交替使用而受到组织特异性调节。为了阐明组织特异性表达的调控机制,制备了携带由人芳香化酶基因的多个启动子控制的报告基因(β-半乳糖苷酶)的人源化TG小鼠。该报告基因在TG小鼠卵巢颗粒细胞、睾丸间质细胞、胎盘、胎肝、皮肤、骨动脉、脂肪组织中均有表达。报告基因在TG小鼠中的表达分布与芳香化酶基因在人中的表达分布完全相同。此外,TG小鼠组织中替代外显子1a、1b、1c和1d的组织偏好性也与人相同。这些结果表明,该人源化TG小鼠是用于分析人芳香族蛋白基因的组织特异性表达的有用的模型动物。少

项目成果

期刊论文数量(60)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Takeyama, J.: "Expression and cellular localization of estrogen receptor a and βin the human fetus"J.Clin.Endocrinol.Metab.. 86. 2258-2262 (2001)
Takeyama, J.:“人类胎儿中雌激素受体 a 和 β 的表达和细胞定位”J.Clin.Endocrinol.Metab.. 86. 2258-2262 (2001)
  • DOI:
  • 发表时间:
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  • 影响因子:
    0
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  • 通讯作者:
Azcoitia, I.: "Brain aromatase is neuroprotective"J.Neurobiol.. 47. 318-329 (2001)
Azcoitia, I.:“脑芳香酶具有神经保护作用”J.Neurobiol.. 47. 318-329 (2001)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Harada, N.: "Localized expression of aromatase in human vascular tissues"Circulation Research. 84. 1285-1291 (1999)
Harada, N.:“芳香酶在人体血管组织中的局部表达”循环研究。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Yamada, K.: "A GCM motif protein is involved in placenta-specific expression of human aromatase gene"Journal of Biological Chemistry. 274. 32279-32286 (1999)
Yamada, K.:“GCM 基序蛋白参与人芳香酶基因的胎盘特异性表达”生物化学杂志。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Utsumi, T.: "Steroid sulfatase expression is an independent predictor of reccurrence in human breast cancer"Cancer Research. 59. 377-381 (1999)
Utsumi, T.:“类固醇硫酸酯酶表达是人类乳腺癌复发的独立预测因子”癌症研究。
  • DOI:
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  • 影响因子:
    0
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HARADA Nobuhiro其他文献

HARADA Nobuhiro的其他文献

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{{ truncateString('HARADA Nobuhiro', 18)}}的其他基金

Challenge to compact, intense, and repetitive light source by using liquid metal
使用液态金属挑战紧凑、强烈和重复的光源
  • 批准号:
    24656184
  • 财政年份:
    2012
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Epigenetic regulation of aromatase gene by changes of chromatin structure
染色质结构变化对芳香酶基因的表观遗传调控
  • 批准号:
    22591019
  • 财政年份:
    2010
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Metabolic regulation of estrogen-synthesizing enzymes by post-translational modification
翻译后修饰对雌激素合成酶的代谢调节
  • 批准号:
    18591034
  • 财政年份:
    2006
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Study on the protection against estrogen-dependent cancer
预防雌激素依赖性癌症的研究
  • 批准号:
    12213132
  • 财政年份:
    2000
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
Experiments on High-Efficiency MHD Generation without Alkali Metal Seed
无碱金属种子高效磁流体产生实验
  • 批准号:
    11450109
  • 财政年份:
    1999
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Study on health
健康研究
  • 批准号:
    10557200
  • 财政年份:
    1998
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular mechanism of aberrant expression of estrogen synthetase in the age-related diseases
年龄相关性疾病中雌激素合成酶异常表达的分子机制
  • 批准号:
    09671080
  • 财政年份:
    1997
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
HIGH EFFICIENCY MHD POWER GENERATION WITHOUT USING ALKALIMETAL
无需使用碱金属即可实现高效率 MHD 发电
  • 批准号:
    08455131
  • 财政年份:
    1996
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Analysis on the transcriptional regulation mechanism of aromatase gene
芳香酶基因转录调控机制分析
  • 批准号:
    02680163
  • 财政年份:
    1990
  • 资助金额:
    $ 8.9万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

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Generating a novel conditional knockout mouse for a super-enhancer that controls cytokine responsiveness
生成一种新型条件敲除小鼠,用于控制细胞因子反应的超级增强子
  • 批准号:
    10740932
  • 财政年份:
    2023
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    10642313
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    2023
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Neuroprotective Effects of Physical Exercise in a Snf2h Knockout Mouse of Retinal Degeneration
体育锻炼对视网膜变性 Snf2h 基因敲除小鼠的神经保护作用
  • 批准号:
    466983
  • 财政年份:
    2021
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    $ 8.9万
  • 项目类别:
    Studentship Programs
The Jackson Laboratory Knockout Mouse Production and Phenotyping Project (JAX KOMP2)
杰克逊实验室基因敲除小鼠生产和表型项目 (JAX KOMP2)
  • 批准号:
    10386984
  • 财政年份:
    2021
  • 资助金额:
    $ 8.9万
  • 项目类别:
The Jackson Laboratory Knockout Mouse Production and Phenotyping Project (JAX KOMP2)
杰克逊实验室基因敲除小鼠生产和表型项目 (JAX KOMP2)
  • 批准号:
    10431514
  • 财政年份:
    2021
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Development of Microglia Knockout Mouse
小胶质细胞敲除小鼠的研制
  • 批准号:
    10040196
  • 财政年份:
    2020
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    $ 8.9万
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Characterization of the prolactin inducible protein, PIP, knockout mouse model PIP KO-CRISPR
催乳素诱导蛋白 PIP、敲除小鼠模型 PIP KO-CRISPR 的表征
  • 批准号:
    540048-2019
  • 财政年份:
    2019
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    $ 8.9万
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    University Undergraduate Student Research Awards
Neuroglobin in the Retina. Use of a Knockout Mouse for Functional assessment / Phenotyping and examining Human relevance, towards Neuroprotection.
视网膜中的神经球蛋白。
  • 批准号:
    MR/T005319/1
  • 财政年份:
    2019
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    $ 8.9万
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    Research Grant
Transgenic/Knockout Mouse Shared Resource
转基因/基因敲除小鼠共享资源
  • 批准号:
    9483643
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    2018
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Study of motile ciliogenesis in vertebrates using Hoatzin knockout mouse
使用 Hoatzin 基因敲除小鼠研究脊椎动物活动纤毛发生
  • 批准号:
    18K06824
  • 财政年份:
    2018
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  • 项目类别:
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