Generation of disease model mice by the alteration of transcription factors regulating immune responses
通过改变调节免疫反应的转录因子产生疾病模型小鼠
基本信息
- 批准号:07557024
- 负责人:
- 金额:$ 6.08万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (A)
- 财政年份:1995
- 资助国家:日本
- 起止时间:1995 至 1997
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The purpose of this study is to regulate the immune responses in vitro and in vivo by the alteration of the function of the transcription factors NF-AT and STAT,which are involved in the regulation of immune responses.We have isolated human NF-AT (NF-ATp/c/x) genes at the beginning of this research program, and during this study we isolated murine counterparts. Among the NF-AT family members, we focused on human and mouse NF-ATx for the analysis and alteration of its function. First, we performed domain mapping of human NF-ATx, and identified several distinct functional domains including the DNA binding domain, AP-1 interaction domain, transactivation domain CN-regulated inhibitory domain (CRI). For CRI sequence, specially deletion of this domain, resulted in nuclear translocation independent of calcium signaling. Next, we identified the calcineurin binding domain (CNBR) of mouse NF-ATx, and found that the over-expression of CNBR protein fragment inhibited NF-AT site calcineurin binding domain acted as a dominant negative mutant that prevents mNF-ATx-mediated gene activation.STAT6 has been shown to be required for mejor IL-4 responses. We constructed a conditionally active form of STAT6 by fusing STAT6 to a modified form of the hormone binding domain of the mouse estrogen receptor. This protein activates a specific receptor construct in response to the bestradiol analog 4-Hydroxy-tamoxifen. We also succeeded in the regulation of GM-CSF-induced response of BAF/3 cells by using a dominant negative mutant of JAK2, which is known to act upstream of STAT proteins.Mutant forms of NF-ATx and STAT6 derived from the above study will be useful fox the regulation of immune responses. We are now planning to generate transgenic mice expressing these mutants for the analysis of the effects of these mutants in vivo.
这项研究的目的是通过改变转录因子的功能NF-AT和STAT的功能来调节体外和体内的免疫反应,这与免疫反应的调节有关。我们在这项研究计划开始时具有分离的人NF-AT(NF-ATP/C/C/X)基因,在这项研究的研究开始时,在这项研究中,以及在这项研究中,我们分离了我们分离的Murine Murine Counterparts。在NF-AT家族成员中,我们专注于人类和小鼠NF-ATX,以分析和改变其功能。首先,我们进行了人类NF-ATX的域映射,并确定了几个不同的功能域,包括DNA结合结构域,AP-1相互作用域,反式激活结构域CN调节的抑制域(CRI)。对于CRI序列,该结构域特别缺失,导致核易位独立于钙信号传导。接下来,我们鉴定了小鼠NF-ATX的钙调神经蛋白结合结构域(CNBR),发现CNBR蛋白片段的过表达抑制了NF-AT位点钙化蛋白结合结构域的抑制作用,该结合结构域被阻止是MNF-ATX介导的基因激活的主要负突变体,该突变体已显示为Mejor.StAT6所需要的MeJor-4-4-4-4-4响应。我们通过将STAT6融合到小鼠雌激素受体的激素结合结构域的修饰形式中,构建了STAT6的有条件活跃的形式。该蛋白质可激活特定的受体构建体,以响应BestRadiol类似物4-羟基tamoxifen。我们还通过使用JAK2的显性阴性突变体来调节GM-CSF诱导的BAF/3细胞反应,该突变体已知可以在STAT蛋白上游起作用。NF-ATX和STAT6从上述研究中得出的Mutant形式将是有用的FOX,将是对免疫反应的调节。现在,我们计划生成表达这些突变体的转基因小鼠,以分析这些突变体在体内的作用。
项目成果
期刊论文数量(23)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Itoh, T., Liu, R., Yokota, T., Arai, K.and Watanabe, S.: "Definition of the role of tyrosin residues of the common b subunit regulating multiple signaling pathways of GM-CSF recepter." Mol.Cell.Biol.18,3. 742-752 (1998)
Itoh, T.、Liu, R.、Yokota, T.、Arai, K. 和 Watanabe, S.:“共同 b 亚基酪氨酸残基调节 GM-CSF 受体多种信号通路的作用的定义。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Watanabe,S., et al: "Characterization of cis-regulatory elementsof the c-myc promoter responding to human GM-CSF or mouse IL-3 in mouse proB cell line BA/F3 cells expressing the human GM-CSF" Mol. Biol. Cell. 6. 627-636 (1995)
Watanabe,S. 等人:“表达人 GM-CSF 的小鼠 proB 细胞系 BA/F3 细胞中响应人 GM-CSF 或小鼠 IL-3 的 c-myc 启动子顺式调控元件的表征”Mol。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Nishinakamura, R., et al: "Mice deficient for the IL-3/GM-CSF/IL-5 receptor exhibit lung pathology and impaired immune response" Immunity. 2. 211-222 (1995)
Nishinakamura, R. 等人:“IL-3/GM-CSF/IL-5 受体缺陷的小鼠表现出肺部病理学和免疫反应受损”。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Itoh,T.et al: "Definition of the role of tyrosin residues of the common β subunit regulating multiple signaling pathways of GM-CSF recepter." Mol.Cell.Biol.18・3. 742-752 (1998)
Itoh, T. 等人:“常见 β 亚基酪氨酸残基调节 GM-CSF 受体多种信号传导途径的作用的定义。”Mol.Cell.Biol.18·3 (1998)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Watanabe, S.et al: "Characterization of cis-acting sequences and trans-acting signals regulating egr-l and c-fos promoters through the GM-CSF recepter in BA/F3 cells." Blood. 89. 1197-1206 (1997)
Watanabe, S.等人:“BA/F3 细胞中通过 GM-CSF 受体调节 egr-1 和 c-fos 启动子的顺式作用序列和反式作用信号的表征。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
ARAI Ken-ichi其他文献
ARAI Ken-ichi的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('ARAI Ken-ichi', 18)}}的其他基金
Joint study on DNA replication and checkpoint control
DNA复制和检查点控制的联合研究
- 批准号:
11694247 - 财政年份:1999
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Studies on regulation of mitotic DNA replication and meiosis by novel Cdc7-related kinase complexes
新型Cdc7相关激酶复合物调控有丝分裂DNA复制和减数分裂的研究
- 批准号:
10480164 - 财政年份:1998
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Analyses of cytokine gene expression by helper T cell subsets : role of NFAT-mediated gene activation and subset-specific regulatory mechanism.
辅助 T 细胞亚群的细胞因子基因表达分析:NFAT 介导的基因激活的作用和亚群特异性调节机制。
- 批准号:
08457103 - 财政年份:1996
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Joint study on regulation of cell profferation by cytokines
细胞因子调控细胞增殖的联合研究
- 批准号:
07044230 - 财政年份:1995
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for international Scientific Research
Development of high-level expression vectors in embryonic and hematopoietic stem cells and generati of GM-CSF and IL-3 of receptor transgenic mice
胚胎干细胞和造血干细胞高水平表达载体的研制及受体转基因小鼠GM-CSF和IL-3的产生
- 批准号:
04559003 - 财政年份:1992
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research (B)
Regulation of IL-3 and GM-CSF genes and their receptors
IL-3 和 GM-CSF 基因及其受体的调节
- 批准号:
04044054 - 财政年份:1992
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for international Scientific Research
Gene expression and DNA replication triggered by growth factors and their receptors
生长因子及其受体触发的基因表达和 DNA 复制
- 批准号:
02404086 - 财政年份:1990
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for General Scientific Research (A)
Denaturation and Its Regulation of Muscular Protein in Marine Animals induced by Storage and Processing as Foodstuff.
食品储存和加工引起的海洋动物肌肉蛋白变性及其调控。
- 批准号:
59470114 - 财政年份:1984
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
相似国自然基金
PARP-1/NF-AT依赖的乳酸代谢重编程诱导慢性淋巴细胞白血病CD8+T细胞耗竭的机制研究
- 批准号:82370195
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
Wnt5a/Ca2+/NF-AT信号通路通过调节Coro1A-Miro细胞器间紧密连接促进口腔鳞癌侵袭的分子机制
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
Wnt5a/Ca2+/NF-AT信号通路通过调节Coro1A-Miro细胞器间紧密连接促进口腔鳞癌侵袭的分子机制
- 批准号:82203790
- 批准年份:2022
- 资助金额:30.00 万元
- 项目类别:青年科学基金项目
相似海外基金
Defining Sex-Specific Systemic and Gut Inflammatory Profiles in People Living with HIV
定义艾滋病毒感染者的性别特异性全身和肠道炎症特征
- 批准号:
10619980 - 财政年份:2023
- 资助金额:
$ 6.08万 - 项目类别:
Investigating the mechanistic contribution of Cav1.2 channels in extinction of cocaine-associated memories
研究 Cav1.2 通道在可卡因相关记忆消退中的机制贡献
- 批准号:
10591507 - 财政年份:2022
- 资助金额:
$ 6.08万 - 项目类别:
The molecular mechanisms of astrocytes-neurons interaction in the morphine use disorder
吗啡使用障碍中星形胶质细胞-神经元相互作用的分子机制
- 批准号:
10487821 - 财政年份:2022
- 资助金额:
$ 6.08万 - 项目类别:
Investigating the mechanistic contribution of Cav1.2 channels in extinction of cocaine-associated memories
研究 Cav1.2 通道在可卡因相关记忆消退中的机制贡献
- 批准号:
10366896 - 财政年份:2022
- 资助金额:
$ 6.08万 - 项目类别:
Contributions of astrocyte RelA signaling in aging-related neurodegenerative sequelae following TBI
星形胶质细胞 RelA 信号传导在 TBI 后衰老相关神经退行性后遗症中的作用
- 批准号:
10536667 - 财政年份:2021
- 资助金额:
$ 6.08万 - 项目类别: