Characterization of mice lacking functional phospholipid hydroperoxide glutathione peroxidase (PHGPx): tissue specific gene targeting
缺乏功能性磷脂氢过氧化物谷胱甘肽过氧化物酶 (PHGPx) 的小鼠的特征:组织特异性基因靶向
基本信息
- 批准号:5366945
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Priority Programmes
- 财政年份:2002
- 资助国家:德国
- 起止时间:2001-12-31 至 2007-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
During the last years we have cloned, by expression cloning, the phospholipid hydroperoxide glutathione peroxidase gene (PHGPx) as a gene that protects Burkitt's lymphoma cells from apoptosis. PHGPx is a selenoenzyme involved in redox metabolism. Since the redox metabolism plays a critical role in the regulation of apoptosis, a knock-out (k.o.) approach of the PHGPx gene in mice has been started. Because there was no way of anticipating the importance of the PHGPx gene for survival and fertility nor of predicting the redundancy of the enzymatic redox systems, several strategies were followed in parallel including a straight k.o. and a conditional k.o. Neither of both approaches gave rise to germ line transmission of the targeted PHGPx allele. Another attempt to generate a conditional k.o. using a modified strategy became necessary when the group of Behne (Berlin) and our group discovered a novel form of PHGPx carrying an alternative exon that had been destroyed in the first attempt to generate a conditional k.o. This novel form of PHGPx encodes a novel sperm-specific nuclear form of PHGPx that very likely plays a crucial role in chromatin condensation of sperm nuclei. While the PHGPx k.o. was in progress, the groups of Ursini and Flohé have found still another function of PHGPx and have identified PHGPx as a major constituent of the capsule of sperm mitochondria. The second conditional k.o. strategy was successful yielding mice with a loxP flanked (floxed) PHGPx allele in the germ line. In the novel funding period we are first aiming to characterize molecularly the messenger RNA of the novel PHGPx including the transcription start site. Our second and major aim is to generate and characterize mice lacking a functional PHGPx gene in different tissues. As a first step, mice hemizygous for PHGPx shall be generated by crossing mice with a floxed PHGPx allele to "deleter" mice expressing the Cre recombinase ubiquitously, and the phenotype of the hemizygous mice shall be studied. Particular interest is directed to the question whether hemizygosity is associated with male infertility and testicular atrophy. As a second step, we shall delete the second PHGPx gene in a tissue-specific manner. Special emphasis will be devoted to the analysis of the PHGPx null phenotype in brain, endothelium and testis. By crossing the mice with the floxed PHGPx allele with mice expressing Cre during different stages of spermatogenesis the question will be answered at which stage of spermatogenesis PHGPx is required and which function it serves.
在过去的几年中,我们已经克隆,表达克隆,磷脂氢过氧化物谷胱甘肽过氧化物酶基因(PHGPx)作为一个基因,保护伯基特淋巴瘤细胞凋亡。PHGPx是参与氧化还原代谢的硒酶。由于氧化还原代谢在细胞凋亡的调节中起关键作用,因此敲除(k.o.)PHGPx基因在小鼠中的研究已经开始。因为没有办法预测PHGPx基因对存活和生育力的重要性,也没有办法预测酶促氧化还原系统的冗余,所以平行地遵循几种策略,包括直接k.o.和条件k.o.这两种方法都没有引起靶向PHGPx等位基因的生殖系传播。又一次尝试生成条件k.o.当Behne(柏林)的小组和我们的小组发现了携带在第一次尝试产生条件性k.o.这种新形式的PHGPx编码一种新的精子特异性核形式的PHGPx,很可能在精子核的染色质凝聚中起着至关重要的作用。虽然PHGPx k.o.在进行中,Ursini和Flohé的小组发现了PHGPx的另一种功能,并确定PHGPx是精子线粒体囊的主要成分。第二个条件k.o.该策略成功地产生了在生殖系中具有loxP侧翼(floxed)PHGPx等位基因的小鼠。在新的资助期内,我们的目标首先是从分子上表征新PHGPx的信使RNA,包括转录起始位点。我们的第二个主要目的是产生和表征在不同组织中缺乏功能性PHGPx基因的小鼠。作为第一步,应通过将具有floxed PHGPx等位基因的小鼠与普遍表达Cre重组酶的“删除”小鼠杂交来产生PHGPx半合子小鼠,并应研究半合子小鼠的表型。特别感兴趣的是半合子是否与男性不育和睾丸萎缩有关的问题。作为第二步,我们将以组织特异性方式删除第二个PHGPx基因。特别强调将致力于PHGPx无效表型在脑,内皮和睾丸的分析。通过将具有floxed PHGPx等位基因的小鼠与在精子发生的不同阶段表达Cre的小鼠杂交,将回答在精子发生的哪个阶段需要PHGPx以及它起什么作用的问题。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
Professor Dr. Georg Wilhelm Bornkamm其他文献
Professor Dr. Georg Wilhelm Bornkamm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 }}
相似国自然基金
脂滴聚集型小胶质细胞介导的髓鞘病变促进小鼠抑郁样行为及其机制研究
- 批准号:82371528
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
孤独症动物模型(Fmr1 KO mice)脑功能网络的时空特性研究
- 批准号:31171025
- 批准年份:2011
- 资助金额:60.0 万元
- 项目类别:面上项目
MALT 淋巴瘤发病分子机理研究
- 批准号:81071626
- 批准年份:2010
- 资助金额:35.0 万元
- 项目类别:面上项目
肿瘤DNA低甲基化发生分子机理及其对白血病发病重要性的研究
- 批准号:30872933
- 批准年份:2008
- 资助金额:36.0 万元
- 项目类别:面上项目
相似海外基金
Characterization of mechanisms responsible for the cardiac dysfunction in mice lacking natriuretic peptide receptor A.
缺乏利尿钠肽受体 A 的小鼠心脏功能障碍机制的表征。
- 批准号:
476738 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Fellowship Programs
Differences in eating behavior in mice lacking ghrelin receptors in AGRP neurons
AGRP神经元中缺乏生长素释放肽受体的小鼠饮食行为的差异
- 批准号:
573532-2022 - 财政年份:2022
- 资助金额:
-- - 项目类别:
University Undergraduate Student Research Awards
Single-cell epigenomic phenotyping of IMPC-generated mouse lines lacking chromatin regulators
IMPC 生成的缺乏染色质调节因子的小鼠系的单细胞表观基因组表型分析
- 批准号:
10656250 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Single-cell epigenomic phenotyping of IMPC-generated mouse lines lacking chromatin regulators
IMPC 产生的缺乏染色质调节因子的小鼠系的单细胞表观基因组表型分析
- 批准号:
10406328 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Examining food motivation in mice lacking ghrelin receptors in Hypothalamic AGRP neurons
检查下丘脑 AGRP 神经元中缺乏生长素释放肽受体的小鼠的食物动机
- 批准号:
564188-2021 - 财政年份:2021
- 资助金额:
-- - 项目类别:
University Undergraduate Student Research Awards
Single-cell epigenomic phenotyping of IMPC-generated mouse lines lacking chromatin regulators
IMPC 产生的缺乏染色质调节因子的小鼠系的单细胞表观基因组表型分析
- 批准号:
10211504 - 财政年份:2021
- 资助金额:
-- - 项目类别:
The analysis of vasculopathy in systemic sclerosis with the mice lacking the Fli1 gene in macrophages
巨噬细胞Fli1基因缺失小鼠系统性硬化症血管病变分析
- 批准号:
20K22972 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Research Activity Start-up
Mechanism underlying ectopic calcification of the mandibular symphysis in mice lacking ENT1
ENT1缺失小鼠下颌联合异位钙化的机制
- 批准号:
364455 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Studentship Programs
IMPC: Cognitive and ethological characterisation of mice lacking melatonin MT2 receptors
IMPC:缺乏褪黑素 MT2 受体的小鼠的认知和行为学特征
- 批准号:
MR/P024130/1 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Research Grant
Phenotype analysis of mice lacking SNARE protein using a novel 3D imaging method; CoMBI.
使用新型 3D 成像方法对缺乏 SNARE 蛋白的小鼠进行表型分析;
- 批准号:
16K08460 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)