GENETIC COMPLEMENTATION OF A MOUSE MODEL FOR PWS

PWS 小鼠模型的遗传互补

• 批准号: 2884429
• 负责人: CAMILYNN I BRANNAN
• 金额: $ 26.05万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-17 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2884429
• 关键词: Prader Willi syndrome; behavior disorders; biological models; brain disorders; disease /disorder etiology; gene complementation; gene expression; genetic mapping; genetically modified animals; laboratory mouse; medical complication; model design /development; transfection

DESCRIPTION: (Adapted from investigator's abstract) This new proposal outlines a series of complementation experiments of a mouse model of Prader-Willi syndrome, which was previously constructed by the investigator. The clinically distinct genetic disorders Prader-Willi (PWS) and Angelman (AS) syndromes arise from opposite patterns of genomic imprinting of human chromosome 15q11-q13. PWS results from loss of paternal gene expression, and AS results from a loss of maternal gene expression. This proposal is based on the finding that while there is a class of human AS patients, which have point mutations in a single causative gene, a similar class of PWS patients has not been identified. This suggests that PWS is a contiguous gene syndrome, caused by the lack of expression of two or more imprinted genes. Individual knock-out mutations created in each of the four genes identified, as candidates for PWS have not revealed a phenotype in mice. The investigator has recently created a deletion mutation involving a global regulatory element, called the Imprinting Center, and produced a mouse model for PWS. In this model, all four of the PWS candidate genes are silenced. The first specific aim is to take advantage of this mouse model to test the hypothesis that two or more genes are responsible for PWS. The strategy will be to determine which combination of the candidate genes when expressed as transgenes are able to complement the PWS mouse model. The second specific aim is to extend this complementation assay to investigate the anatomical sites of the various PWS clinical features by using tissue-restricted expression of the complementing transgene(s).

描述：（改编自研究者的摘要）这个新提案概述了