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

• 批准号: 8507999
• 负责人: ANDREW P. MCMAHON
• 金额: $ 15.94万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 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/8507999
• 关键词: GUDMAP2; Production; Mouse; Strains; Gene

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“泌尿生殖解剖项目 (GUDMAP)”的回应。 GUDMAP 计划 (GUDMAP II) 的延续旨在定义下尿路的分子解剖结构。我们建议培育一系列新型小鼠品系，使通过本次 RFA 资助的团体能够识别、分离和基因操纵靶细胞类型，以更好地了解这些细胞及其后代在下尿路发育中的作用。我们预计这些菌株将实现基于抗体的方法，用于器官解剖学的 2 维和 3 维成像、用于基因表达转录分析的细胞分离以及细胞命运分析，以探索下尿路发育和成体器官中的细胞关系。在 Aim1 中，我们将利用由 NIH 资助的 KOMP 计划及其欧洲同行 EUCOMM 创建的广泛的靶向胚胎干 (ES) 细胞库。这些“敲除第一条件等位基因”将作为二次基因靶向的平台，利用双重组酶介导的盒交换方法。在此，新型细胞标记（GPP）和基因组修饰酶（CRE-ERT2）被置于选择用于在感兴趣的细胞群中表达的特定基因的控制下。在目标 2 中，靶向 ES 细胞将用于产生嵌合小鼠，并最终产生含有新标记/修饰等位基因的新型小鼠品系。这些菌株将分发给 GUDMAP II 成员以方便他们的分析，并分发给 NIH 资助的小鼠突变体资源中心，以便分发给生物医学研究界。