GUDMAP2 - Production of Mouse Strains for Gene Anatomy of the Lower Urinary Tract

GUDMAP2 - 用于下尿路基因解剖的小鼠品系的生产

基本信息

批准号：
8730767
负责人：
ANDREW P. MCMAHON
金额：
$ 59.28万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-30 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8730767
关键词：
3-Dimensional Adult Affect Alleles Anatomy Antibodies Archives Atlases Australia Biomedical Research Breeding Cell Line Cell Separation Cells Clinic Clinical Communities Complement Congenital Abnormality Deposition Development Diagnosis Disease Embryo Enterobacteria phage P1 Cre recombinase Enzymes European Functional disorder Funding Future Gene Expression Profiling Gene Targeting Genes Genetic Genetic Recombination Genitourinary system Genome Germ Lines Image Incidence Injection of therapeutic agent International Kidney Knock-out Knockout Mice Knowledge Laboratories LacZ Genes Lead Lower urinary tract Mediating Medical Research Molecular Mouse Strains Mus Mutant Strains Mice Optical Tomography Organ Pediatric Hospitals Pharmaceutical Preparations Population Production Proteins Reporter Research Research Infrastructure Research Personnel Resolution Resources Role Series Southern Blotting Specific Pathogen Frees Stem cells System United States National Institutes of Health Universities Urologic Diseases Work aging population base biological research blastocyst cell type enhanced green fluorescent protein genetic manipulation germ free condition high throughput analysis improved insight interest knock out mouse project member novel novel marker recombinase response tool transcriptome sequencing transmission process urinary

项目摘要

DESCRIPTION (provided by applicant): The proposed research plan is in response to RFA-DK-11-001, "A Genitourinary Anatomy Project (GUDMAP)." This continuation of the GUDMAP initiative (GUDMAP II) aims to define the molecular anatomy of the lower urinary tract. We propose to generate a series of novel mouse strains that will enable groups funded through this RFA to identify, isolate, and genetically manipulate target cell types to better understand the roles of these cells and their descendants in development of the lower urinary tract. We anticipate that the strains will enable antibody-based approaches for 2- and 3-dimensional imaging of organ anatomy, cell isolation for transcriptional analysis of gene expression, and cell fate analysis to explore cell relationships in developing and adult organs of the lower urinary tract. In Aim1, we will make use of the extensive repertoire of targeted embryo stem (ES) cells created by the NIH-funded KOMP initiative and its European counterpart, EUCOMM. These "knock-out first conditional alleles" will serve as a platform for secondary gene-targeting, utilizng a dual recombinase mediate cassette exchange approach. In this, novel cell markers (GPP) and genome modifying enzymes (CRE-ERT2) are placed under the control of specific genes selected for expression in cell populations of interest. In Aim 2, targeted ES cells will be used t generate chimeric mice and ultimately novel mouse strains harboring the new marker/modifier alleles. These strains will be distributed to GUDMAP II members to facilitate their analyses and to NIH-funded Mouse Mutant Resource Centers for distribution to the biomedical research community.

描述（由申请人提供）：拟议的研究计划是对RFA-DK-11-001的响应，“泌尿生殖器解剖项目（GUDMAP）”。 GUDMAP倡议（GUDMAP II）的这种延续旨在定义下尿路的分子解剖结构。我们建议生成一系列新型的小鼠菌株，这些菌株将使通过此RFA资助的组识别，分离和遗传操纵靶细胞类型，以更好地了解这些细胞及其后代在较低尿路发展中的作用。我们预计菌株将实现基于抗体的方法，用于对器官解剖结构的2和3维成像，细胞分离，用于基因表达的转录分析以及细胞命运分析，以探索下尿道的发展和成人器官的细胞关系。在AIM1中，我们将利用由NIH资助的Komp倡议及其欧洲同行Eucomm创建的针对性胚胎茎（ES）细胞的广泛曲目。这些“敲除第一条件等位基因”将作为二级基因靶向的平台，利用双重重组酶介导了盒式盒式盒式交换方法。在此中，新颖的细胞标记（GPP）和基因组修饰酶（CRE-ERT2）被置于选择在感兴趣的细胞群体中选择用于表达的特定基因的控制。在AIM 2中，靶向ES细胞将被t生成嵌合小鼠，并最终带有具有新标记物/修饰符等位基因的新型小鼠菌株。这些菌株将分配给GUDMAP II成员，以促进其分析，并向NIH资助的小鼠突变资源中心分配给生物医学研究界。