Mouse Models of Human PWS/AS Imprinting Center Mutations

人类 PWS/AS 印记中心突变的小鼠模型

• 批准号: 6438424
• 负责人: JAMES L RESNICK
• 金额: $ 24.76万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6438424
• 关键词: Prader Willi syndrome; alleles; animal genetic material tag; disease /disorder model; gene deletion mutation; gene expression; gene mutation; genetic models; genetic regulatory element; genetically modified animals; genomic imprinting; happy puppet syndrome; laboratory mouse; methylation; model design /development; open reading frames; radionuclides; restriction fragment length polymorphism; tissue /cell culture

DESCRIPTION (provided by applicant): Most genes in mammals are expressed equally from the maternally and paternally inherited alleles. However, some genes are imprinted, resulting in selective expression from only one parental allele. One consequence of imprinting is that mutation of the expressed allele results in the absence of a gene product despite the presence of a wild-type, but silent allele. This is the senario involved in the related but clinically distinct genetic disorders Prader-Willi (PWS) and Angelman (AS) syndromes which arise from opposite patterns of genomic imprinting of human chromosome l5q11-q13. Imprinting of this approximately 2 Mb region is regulated by a bipartate Imprinting Center (IC), composed of an AS-IC and a PWS-IC. Over the last several years, we have established the mouse as a model system for studying the regulation of 15q11-q13 imprinting, demonstrating that the region upstream and including a portion of the Snrpn gene serves as a PWS-IC. The goal of this renewal application is to take advantage of the mouse to dissect the mechanism of imprinting in this region. Our first specific aim is to investigate the role of the PWS-IC in somatic tissues. The second specific aim is to functionally define the murine AS-IC and investigate its role in gene regulation. The third specific aim is to test predictions of a model that we have recently proposed to explain the regional pattern of parental specific gene expression. The final specific aim is to make use of our newly developed transgenic assay to identify the minimal cis-acting elements responsible for the imprinting of the Snrpn gene. Together, these experiments will greatly increase our understanding of how the IC serves to regulate imprinted gene expression in 15q11-q13.

描述（由申请人提供）：哺乳动物的大多数基因都被表达