权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Streamline assessment of early lethal phenotypes in the mouse

简化小鼠早期致死表型的评估

基本信息

批准号：
10767623
负责人：
Jesse Mager
金额：
$ 16.1万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-08 至 2025-08-31
项目状态：
未结题

项目摘要

Streamline assessment of early lethal phenotypes in the mouse. Although the generation of a loss of function allele at every locus in the mouse genome is well underway, there is a gap in established pipelines for assessment of early lethal phenotypes (as stated in PAR-17-005). Here we propose to continue our efforts to characterize up to 150 early lethal phenotypes occurring between fertilization and organogenesis. As described within, we have instituted an efficient strategy to analyze early lethal phenotypes and have already analyzed more than 100 novel phenotypes. We will provide a tremendous amount of novel data to the scientific community and foster collaborative efforts towards functional annotation of the mammalian genome. The proposed work capitalizes on techniques that our groups perform and publish routinely, maximizing the data generation by eliminating training/troubleshooting steps as well as boosting our individual research programs by providing novel phenotypes of interest. Characterization of knock-out alleles will be invaluable towards understanding genetic pathways and predicting mechanisms of diseases/phenotypes found in adults – in both heterozygotes and homozygous knockouts of genes in gene/protein networks or pathways. We will provide detailed morphogenetic characterization for each mutant phenotype. Characterization of novel gastrulation and preimplantation phenotypes will complement and extend our current morphogenetic understanding of early developmental events. Our proposal dovetails perfectly with existing phenotyping efforts and fills an essential need to characterize early lethal phenotypes towards functional annotation of the genome.

简化小鼠早期致死表型的评估。尽管小鼠基因组中每个基因座的功能缺失等位基因正在顺利生成，但是用于评估早期致死表型的现有管道中的一个缺口（如 PAR-17-005 中所述）。在这里我们建议继续努力描述受精之间发生的多达 150 种早期致死表型和器官发生。如本文所述，我们制定了一种有效的策略来分析早期致死性表型并已经分析了 100 多种新表型。我们将提供大量的向科学界提供新数据，并促进对功能注释的合作努力哺乳动物基因组。拟议的工作利用了我们小组执行和发布的技术通常，通过消除训练/故障排除步骤以及提高我们的能力来最大化数据生成通过提供感兴趣的新颖表型来开展个人研究计划。敲除等位基因的表征将对于理解遗传途径和预测疾病/表型机制具有无价的价值在成人中发现——在基因/蛋白质网络中基因的杂合子和纯合子敲除中或途径。我们将为每个突变表型提供详细的形态发生特征。新型原肠胚形成和植入前表型的表征将补充和扩展我们目前的研究对早期发育事件的形态发生的理解。我们的建议与现有的表型分析工作完美契合，并满足了早期表征的基本需求致死表型对基因组的功能注释。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Streamlined ex vivo and in vivo genome editing in mouse embryos using recombinant adeno-associated viruses.

DOI：
10.1038/s41467-017-02706-7
发表时间：
2018-01-29
期刊：
Nature communications
影响因子：
16.6
作者：
Yoon Y;Wang D;Tai PWL;Riley J;Gao G;Rivera-Pérez JA
通讯作者：
Rivera-Pérez JA

Exosome complex components 1 and 2 are vital for early mammalian development.

外泌体复合物成分 1 和 2 对于早期哺乳动物发育至关重要。

DOI：
10.1016/j.gep.2023.119346
发表时间：
2024
期刊：
Gene expression patterns : GEP
影响因子：
0
作者：
Srinivasan,Sanjana;He,Xinjian;Mirza,Sarah;Mager,Jesse
通讯作者：
Mager,Jesse

Protein phosphatase 1 regulatory subunit 35 is required for ciliogenesis, notochord morphogenesis, and cell-cycle progression during murine development.

蛋白磷酸酶 1 调节亚基 35 是小鼠发育过程中纤毛发生、脊索形态发生和细胞周期进展所必需的。

DOI：
10.1016/j.ydbio.2020.06.011
发表时间：
2020
期刊：
Developmental biology
影响因子：
2.7
作者：
Archambault,Danielle;Cheong,Agnes;Iverson,Elizabeth;Tremblay,KimberlyD;Mager,Jesse
通讯作者：
Mager,Jesse

KAT-Independent Gene Regulation by Tip60 Promotes ESC Self-Renewal but Not Pluripotency.