Generation and application of mtDNA knockout mice models of aging
线粒体DNA敲除小鼠衰老模型的构建及应用
基本信息
- 批准号:10832001
- 负责人:
- 金额:$ 2.05万
- 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:1998
- 资助国家:日本
- 起止时间:1998 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Mice possessing pathogenic mutant mitochondrial DNA (mtDNA) would provide ideal systems for studying exactly how mutant mtDNAs are transmitted and distributed in tissues resulting in expression of mitochondrial diseases, but no effective procedures are available for their generation. Isolation of mtDNA-less (ρ^0) mouse cells enabled us to trap mouse mutant mtDNAs that had accumulated in somatic tissues into mtDNA repopulated ρ^0 cells (cybrids). We could isolate respiration-deficient cybrids with a deletion mutant mtDNA and introduce it into fertilized eggs. The mutant mtDNA was transmitted maternally, and its accumulation induced mitochondrial dysfunction in various tissues. Moreover, most of these mice unexpectedly died as a consequence of renal failure, suggesting the involvement of mtDNA mutations in the pathogeneses of new diseases.
拥有致病突变线粒体DNA(MtDNA)的小鼠将为研究突变mtDNA如何在组织中传递和分布导致线粒体疾病的表达提供理想的系统,但目前还没有有效的方法来产生它们。线粒体DNA缺失(ρ^0)小鼠细胞的分离使我们能够将积累在体细胞组织中的突变的小鼠线粒体DNA捕获到线粒体DNA重新繁殖的ρ^0细胞(胞体)中。我们可以用缺失突变体mtDNA分离出呼吸缺陷的线虫,并将其引入受精卵。突变的mtDNA通过母体传播,其积累导致各种组织的线粒体功能障碍。此外,这些小鼠中的大多数都意外死于肾功能衰竭,这表明mtDNA突变参与了新疾病的发病机制。
项目成果
期刊论文数量(32)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Eizo Ohkubo: "A patient with type 2 diabetes mellitus associated with mutations in sensing receptor gene and mitochondrial DNA"Biochem.Biophys.Res.Commun.. 278. 808-813 (2000)
Eizo Ohkubo:“与传感受体基因和线粒体 DNA 突变相关的 2 型糖尿病患者”Biochem.Biophys.Res.Commun.. 278. 808-813 (2000)
- DOI:
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- 影响因子:0
- 作者:
- 通讯作者:
Ito, S.: "Functional integrity of mitochondrial genomes in human platelets and autopsied brain tissues from aged patients with Alzheimer's disease."Proc. Natl. Acid. Sci. USA. 96. 2099-2103 (1999)
Ito, S.:“人类血小板和老年阿尔茨海默病患者尸检脑组织中线粒体基因组的功能完整性。”Proc。
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- 影响因子:0
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Matsuoka, R.: "A mitochondrial DNA mutation co-segregates with the pathophysiological U wave."Biochem. Biophys. Res. Commun.. 257. 228-233 (1999)
Matsuoka, R.:“线粒体 DNA 突变与病理生理学 U 波共分离。”Biochem。
- DOI:
- 发表时间:
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- 影响因子:0
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- 通讯作者:
Kimiko Inouc: "Generation of mice with mitochondrial dysfunction by introducing mouse mtDNA carrying a deletion into zygotes"Nature Genetics. 26. 176-181 (2000)
Kimiko Inouc:“通过将携带缺失的小鼠 mtDNA 引入受精卵来产生线粒体功能障碍的小鼠”《自然遗传学》。
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- 影响因子:0
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HAYASHI Jun-ichi其他文献
HAYASHI Jun-ichi的其他文献
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{{ truncateString('HAYASHI Jun-ichi', 18)}}的其他基金
Analysis of entire physiological roles of mammalian mtDNA by generation of mice carrying various pathogenic mutations
通过产生携带各种致病突变的小鼠来分析哺乳动物线粒体DNA的整个生理作用
- 批准号:
19100007 - 财政年份:2007
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (S)
Studies on pathogenesis and gene therapy using mice with the mutated mtDNA in tRNA genes
tRNA基因mtDNA突变小鼠的发病机制和基因治疗研究
- 批准号:
14035101 - 财政年份:2002
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
Generation and application of mtDNA knockout mice as models for mitochondrial diseases
线粒体DNA敲除小鼠线粒体疾病模型的产生及应用
- 批准号:
10358018 - 财政年份:1998
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Analyzes of genes responsible for aging and the pathogenesis of diabetes by isolation of transgenic mice with pathogenic mtDNA mutation
通过分离具有致病性 mtDNA 突变的转基因小鼠来分析导致衰老和糖尿病发病机制的基因
- 批准号:
07458226 - 财政年份:1995
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Isolation of mtDNA knock-out mice by introduction of disease-related mtDNA mutation
通过引入疾病相关 mtDNA 突变来分离 mtDNA 敲除小鼠
- 批准号:
06557040 - 财政年份:1994
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
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21590349 - 财政年份:2009
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21390459 - 财政年份:2009
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7942870 - 财政年份:2009
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mtDNA mutation/heteroplasmy: a sensitive functional biomarker of oxidative stress
mtDNA 突变/异质性:氧化应激的敏感功能生物标志物
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Analyzes of genes responsible for aging and the pathogenesis of diabetes by isolation of transgenic mice with pathogenic mtDNA mutation
通过分离具有致病性 mtDNA 突变的转基因小鼠来分析导致衰老和糖尿病发病机制的基因
- 批准号:
07458226 - 财政年份:1995
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Isolation of mtDNA knock-out mice by introduction of disease-related mtDNA mutation
通过引入疾病相关 mtDNA 突变来分离 mtDNA 敲除小鼠
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06557040 - 财政年份:1994
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$ 2.05万 - 项目类别:
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