REGULATION OF TRANSGENE EXPRESSION

转基因表达的调节

• 批准号: 6289909
• 负责人: Raymond W Tennant
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6289909
• 关键词: cell differentiation; chemical carcinogenesis; cutaneous papilloma; gene induction /repression; gene mutation; genetically modified animals; guanine nucleotide binding protein; in situ hybridization; laboratory mouse; neoplasm /cancer genetics; northern blottings; oncogenes; phorbols; polymerase chain reaction; skin; transforming growth factors; wound healing

Genetically initiated Tg.AC transgenic mice carry a transgene consisting of an oncogenic v-Ha-ras coding region flanked 5 by a mouse zetaglobin promoter and 3 by an SV-40 polyadenylation sequence. Located proximal to the centromere on chromosome 11, the transgene is transcriptionally silent until activated by full thickness wounding, UV light, or chemical carcinogens. This discriminating tumorigenic response does not occur when Tg.AC mice are treated with structurally similar non-carcinogenic chemicals. Expression of the transgene is a required early event that drives cellular proliferation resulting in clonal expansion and tumor formation. Genetic and epigenetic mechanism may contribute to this induced response. A very unique and specific assemblage of cis regions and transcription factors intrinsic to the tumorigenic process are required to activate the transgene following treatments with carcinogens. Our laboratory is interested in elucidating the induced tumorigenic response in Tg.AC v-Ha-ras transgenic mice. Our approach is to utilize molecular, genetic and biochemical techniques to identify the transcriptional control regions and the associated factors.

遗传起始的Tg.AC转基因小鼠携带由致癌v-Ha-ras编码区组成的转基因，所述致癌v-Ha-ras编码区5侧接小鼠zetaglobin启动子，3侧接SV-40多聚腺苷酸化序列。该转基因位于11号染色体上的着丝粒附近，在转录上沉默，直到被全层创伤、紫外线或化学致癌物激活。当用结构相似的非致癌化学物质处理Tg.AC小鼠时，不会发生这种有区别的致瘤反应。转基因的表达是驱动细胞增殖导致克隆扩增和肿瘤形成所需的早期事件。遗传和表观遗传机制可能有助于这种诱导的反应。一个非常独特的和特定的组合的顺式区域和转录因子固有的致瘤过程中需要激活的转基因治疗致癌物。本实验室对阐明Tg.AC v-Ha-ras转基因小鼠诱导的致瘤反应感兴趣。我们的方法是利用分子、遗传和生物化学技术来鉴定转录控制区和相关因子。