Neuropathogenic abnormalities in transgenic mice expressing transcription factors of neurotropic viruses in the central nervous system
中枢神经系统中表达嗜神经病毒转录因子的转基因小鼠的神经病理性异常
基本信息
- 批准号:11660291
- 负责人:
- 金额:$ 2.43万
- 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:1999
- 资助国家:日本
- 起止时间:1999 至 2001
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
To assess the neuropathogenic potentials of transcription factors of neurotropic viruses, we have generated several transgenic mouse lines.Pseudorabies virus (PRV) infection in animals other than its natural host almost always gives rise to fatal diseases in the central nervous system as a result of infection of peripheral neurons and subsequent to the brain. To study the role of immediate-early protein (IE180) of PRV in neuropathogenicity, we have generated transgenic mouse lines expressing IE180 in a tetracycline-regulated system (Tet-Off System). The transgenic mice showed cerebellar symptoms such as ataxic gait, tremor and motor discoordination. In the transgenic mice, histopathology of the cerebellum was remarkable for a failure of layer formation and reduced cerebellum sizes. Although the IE180 transcripts were detected in all tissues, no histological abnormality was observed in the tissues other than cerebellum. These findings suggest that IE180 affects the cascade of gene expression for development of the murine cerebellum.Borna disease virus infection causes a spectrum of behavioral deficits. To study the role of p24 of BDV in neuropathogenicity, we have generated transgenic mouse lines expressing p24 in astrocytes. The transgenic mice showed enhanced intermale aggressiveness and abnormalities in spatial learning. In the transgenic mice, brain-derived neurotrophic factor and synaptophysin were markedly decreased in hippocampus and cerebellum. These findings suggest that expression and accumulation of p24 in astrocytes creates neurodevelopmental disturbances.
为了研究嗜神经病毒转录因子的神经致病性,我们建立了几种转基因小鼠品系,伪狂犬病病毒(PRV)感染非天然宿主动物后,几乎总是引起中枢神经系统的致命性疾病,其结果是感染外周神经元,继而感染大脑。为了研究PRV的立即早期蛋白(IE 180)在神经致病性中的作用,我们在四环素调节系统(Tet-Off系统)中产生了表达IE 180的转基因小鼠系。转基因小鼠表现出小脑症状,如共济失调步态,震颤和运动失调。在转基因小鼠中,小脑的组织病理学表现为层形成失败和小脑尺寸减小。虽然IE 180转录本检测到所有组织中,没有观察到组织学异常小脑以外的组织。这些发现表明IE 180影响了小鼠小脑发育的基因表达级联反应。博尔纳病病毒感染引起了一系列的行为缺陷。为了研究BDV的p24在神经致病性中的作用,我们已经产生了在星形胶质细胞中表达p24的转基因小鼠品系。转基因小鼠表现出增强的雄性间攻击性和空间学习的异常。在转基因小鼠中,海马和小脑中的脑源性神经营养因子和突触素显著减少。这些发现表明星形胶质细胞中p24的表达和积累造成神经发育障碍。
项目成果
期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Taharaguchi, S.: "Analysis of regulatory functions for the region located upstream from the latency associated transcript (LAT) promoter of pseudorabies virus in cultured cells"Veterinary Microbiology. (印刷中).
Taharaguchi, S.:“培养细胞中伪狂犬病病毒潜伏相关转录本 (LAT) 启动子上游区域的调节功能分析”《兽医微生物学》(正在出版)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Tasaki, T., Taharaguchi, S., Kobayashi, T., Yoshino, S. and Ono, E.: "Inhibition of pseudorabies virus replication by a dominant-negative mutant of early protein 0 expressed in a tetracycline-regulated system"Veterinary Microbiology. (印刷中).
Tasaki, T.、Taharaguchi, S.、Kobayashi, T.、Yoshino, S. 和 Ono, E.:“四环素调节系统中表达的早期蛋白 0 的显性失活突变体对伪狂犬病病毒复制的抑制”兽医微生物学(正在出版)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Ono E.: "Resistance to Pseudorabies Virus Infection in Transgenic Mice Expressing the Chimeric Transgene That Represses the Immediate-Early Gene Transcription"Virology. 262(1). 72-78 (1999)
Ono E.:“表达抑制立即早期基因转录的嵌合转基因的转基因小鼠对伪狂犬病病毒感染的抵抗”病毒学。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Taharaguchi, S.: "A pan-specific promoter activity of the 213bp element of the pseudorabies virus early protein 0 gene in transgenic mice"Archives of Virology. 147・(1). 11-19 (2002)
Taharaguchi,S.:“转基因小鼠中伪狂犬病病毒早期蛋白0基因的213bp元件的泛特异性启动子活性”病毒学档案147·(1)(2002)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
E.Ono, T.Tasaki, T. Kobayashi, S.Taharaguchi, H.Nikami, I.Miyoshi, N.Kasai, J.Arikawa, H.Kida and Y.Shimizu: "Resistance to pseudorabies virus infection in transgenic mice expressing the chimeric transgene that represses the immediate-early gene transcrip
E.Ono、T.Tasaki、T. Kobayashi、S.Taharaguchi、H.Nikami、I.Miyoshi、N.Kasai、J.Arikawa、H.Kida 和 Y.Shimizu:“表达转基因小鼠对伪狂犬病病毒感染的抵抗力
- 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 }}
ONO Etsuro其他文献
ONO Etsuro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('ONO Etsuro', 18)}}的其他基金
Generation of transboundary animal diseases-resistant animals by genetic modification technologies to Rab-GTPases genes
利用Rab-GTP酶基因转基因技术培育跨境动物抗病动物
- 批准号:
20K20577 - 财政年份:2020
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Challenging Research (Pioneering)
Generation of transgenic mice expressing soluble forms of Siglecs as a model for influenza-resistant pigs
表达可溶形式 Siglecs 的转基因小鼠的产生作为抗流感猪的模型
- 批准号:
22380161 - 财政年份:2010
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
GENERATION OF TRANSGENIC MICE EXPRESSING SOLUBLE FORM OF PORCINE NECTIN-1 AS A MODEL FOR PSEUDORABIES-RESISTANT LIVE STOCK
表达可溶形式的猪 NECTIN-1 的转基因小鼠的产生作为抗伪狂犬病家畜的模型
- 批准号:
17580265 - 财政年份:2005
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Generation of Pseudorabies-resistant Animals by Germ-line Transformation
通过种系转化产生抗伪狂犬病动物
- 批准号:
12556048 - 财政年份:2000
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Intracellular immunization against Aujeszky's disease
针对 Aujeszky 病的细胞内免疫
- 批准号:
04660312 - 财政年份:1992
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
相似海外基金
TRANSACTIVATION BY THE PSEUDORABLES VIRUS IEP PROTEIN
伪病毒 IEP 蛋白的反激活
- 批准号:
3130812 - 财政年份:1985
- 资助金额:
$ 2.43万 - 项目类别:
TRANSACTIVATION BY THE PSEUDORABLES VIRUS IEP PROTEIN
伪病毒 IEP 蛋白的反激活
- 批准号:
3130814 - 财政年份:1985
- 资助金额:
$ 2.43万 - 项目类别:
TRANSACTIVATION BY THE PSEUDORABLES VIRUS IEP PROTEIN
伪病毒 IEP 蛋白的反激活
- 批准号:
3130808 - 财政年份:1985
- 资助金额:
$ 2.43万 - 项目类别:
TRANSACTIVATION BY THE PSEUDORABLES VIRUS IEP PROTEIN
伪病毒 IEP 蛋白的反激活
- 批准号:
3130811 - 财政年份:1985
- 资助金额:
$ 2.43万 - 项目类别:
TRANSACTIVATION BY THE PSEUDORABLES VIRUS IEP PROTEIN
伪病毒 IEP 蛋白的反激活
- 批准号:
3130813 - 财政年份:1985
- 资助金额:
$ 2.43万 - 项目类别: