DEVELOPMENTAL CONTROL OF INTRODUCED GENES IN RODENTS

本提案中所述实验的目的是剖析 影响发育调控的分子机制 内源性小鼠逆转录病毒、小鼠乳腺肿瘤病毒的表达 (MTV)并将该病毒对乳腺癌的诱导限制在 乳腺 另一个目标是了解 决定小鼠是否易受MTV诱导的遗传因素 乳腺肿瘤和免疫系统在这一过程中的作用。到 实现这些目标，分子克隆技术，组织 培养物转染研究和转基因小鼠将用于 鉴定MTV长末端重复序列（LTR）内的DNA序列 引导病毒在乳腺中表达。 此外，本发明还 与这些DNA序列相互作用的转录因子将是 克隆并用于研究这些因子在发育中的表达 不同品系小鼠的乳腺和乳腺肿瘤。 最后， MTV LTR开放阅读框（ORF）蛋白的作用，其影响 将评估小鼠中的T细胞库， 不同品系小鼠对MTV诱导的 癌 本提案中概述的实验将使我们能够 开始剖析遗传背景对肿瘤发生的作用。 由MTV启动的过程以及免疫系统在响应 病毒感染和肿瘤发生。 通过扩展，这些实验将 也增加了我们对这些不同组成部分的作用的理解 在人类乳腺癌中。

The objective of the experiments described in this proposal is to dissect the molecular mechanisms which affect the developmental regulation of expression of the endogenous murine retrovirus, mouse mammary tumor Virus (MTV) and limit the induction of mammary carcinomas by this virus to the mammary gland. An additional goal is to achieve an understanding of the genetic factors that determine whether mice are susceptible to MTV-induced mammary tumors and the role of the immune system in this process. To achieve these goals, a combination of molecular cloning techniques, tissue culture transfection studies and transgenic mice will be used to characterize the DNA sequences within the long terminal repeat (LTR) of MTV that direct expression of the virus to the mammary gland. Additionally, the transcription factors that Interact with these DNA sequences will be cloned and used to study expression of these factors in the developing mammary gland of different mouse strains and in mammary tumors. Lastly, the role of the MTV LTR open reading frame (ORF) protein, which influences the T cell repertoire in mice, will be assessed, In both the virus life cycle and in the susceptibility of different strains of mice to MTV-induced carcinomas. The experiments outlined in this proposal will allow us to begin to dissect the contributions of genetic background to the tumorigenic process initiated by MTV and the role of the immune system in responding to viral infection and tumorigenesis. By extension, these experiments will also increase our understanding of the role of these different components in human breast cancer.