TELOMERASE IN DEVELOPMENT SENESCENCE AND NEOPLASIA

描述(改编自调查人员摘要)：这些目标 研究是为了验证端粒假说：细胞衰老 由于端粒重复序列缩短到临界长度而触发 在细胞永生化过程中端粒酶功能的丧失 端粒酶重新激活。这项提案的目标是：i)评估 端粒酶在正常细胞生长发育中的作用 胚胎发生，II)在已建立的器官系统的动态平衡中 成人和iii)确定人类对端粒酶活性的需求 肿瘤。为了实现这些目标，德·皮尼奥博士将利用 编码该基因纯合子为空的基因敲除小鼠模型 端粒酶的基本RNA引物成分。发展与创新 将监测端粒酶缺乏症的生理后果 具有显著再生能力的器官系统。癌症 将通过培育这些小鼠来确定端粒酶缺乏的方面 有几个公认的易患癌症的模型。

DESCRIPTION (adapted from investigator's abstract): The goal of these studies is to test the telomere hypothesis: Cellular senescence is triggered by the shortening of telomere repeats to a critical length due to loss of telomerase function while cellular immortalization involves telomerase reactivation. The objectives of this proposal are : i) to assess the role of telomerase in the growth and development of normal cells during embryogenesis, ii) in the homeostasis of established organ systems of the adult and iii) to determine the requirement for telomerase activity in neoplasia. To achieve these objectives, Dr. De Pinho will make use of a knockout mouse model which is homozygous null for the gene encoding the essential RNA primer component of telomerase. The developmental and physiological consequences of telomerase deficiency will be monitored in organ systems that posses significant regenerative capacity. The cancer aspect of telomerase deficiency will be determined by breeding these mice with several well-established cancer-prone models.