BIOLOGY OF MAMMALIAN HOMEODOMAIN PROTEINS

其功能障碍扰乱苍蝇胚胎发生的大多数蛋白质 共享一个由60个氨基酸组成的特征区域，称为同源结构域。 哺乳动物也同样表达含有同源结构域的蛋白质。基于他们的 核定位，它们与特定DNA序列结合的能力， 以及它们与一些特征良好的转录因子的关系，它是 提示同源结构域蛋白参与基因调控 在哺乳动物中的表达。在我们努力确定其功能的同时 哺乳动物的同源结构域蛋白，我们已经克隆、测序并研究了 小鼠触角虫类基因Hox 1-3-的表达 为了测试体内的生物功能，我们最近培育了转基因小鼠 其包含诱导物的单个或多个(最多25个)拷贝 HOX 1.3转基因。为了控制异位HOX 1.3的表达水平，我们 使用了可诱导的小鼠MXL调控元件作为我们的转基因 启动子允许HOX 1-3在 其诱导物(干扰素或双链RNA)的存在。在……下面 生理条件，即在没有诱导的情况下，小鼠 表达其内源Hox 1.3基因，并在经检测的器官中 Northern分析，很少或根本没有检测到转基因RNA。在 没有转基因诱导，这些小鼠看起来很健康。转基因后 在干扰素或双链RNA的诱导下，小鼠开始 在多种不同的环境中高效表达转基因RNA和蛋白质 器官。此外，静脉注射干扰素 在子宫内携带转基因胚胎的非转基因雌性会导致 我们转基因基因的胎儿诱导性。我们的首要目标是第一 确定在胚胎或出生后发育期间是否以及何时发生 异位表达HOX 1.3有一定效果，然后将其用于体内 用于识别上调或下调的内源性基因的工具 霍克斯1.3。

Most of the proteins whose dysfunction disturbs embryogenesis of the fly share a characteristic stretch of 60 amino acids called the homeodomain. Mammals likewise express homeodomain-containing proteins. Based on their nuclear localization, their capacity to bind to specific DNA sequences, and their relation to some well-characterized transcription factors, it is suggested that homeodomain proteins are involved in regulating gene expression in mammals. In our effort to determine the function of mammalian homeodomain proteins, we have cloned, sequenced, and studied the expression of one of the murine Antennapedia class genes known as Hox 1-3- To test in vivo biofunction, we have recently generated transgenic mice that contain either a single or multiple (up to 25) copies of an inducible Hox 1.3 transgene. To control the levels of ectopic Hox 1.3 expression, we have used the inducible mouse Mxl regulatory element as our transgene promoter which allows the deliberate ubiquitous expression of Hox 1-3 in the presence of its inducers (interferon or double-stranded RNA). Under physiologic conditions, that is, in the absence of induction, the mice express their endogenous Hox 1.3 gene, and in those organs tested by Northern analysis, little or no detectable transgene RNA was found. In the absence of transgene induction, these mice appear healthy. After transgene induction with either interferon or double-stranded RNA, the mice start to express high levels of transgenic RNA and protein in many different organs. In addition, intravenous injection of interferon into non-transgenic females that carry in utero transgenic embryos results in the fetal induction of our transgene. Our primary goal is to first identify if and when during embryonic or postnatal development does ectopic expression of Hox 1.3 have an effect, and then to use this in vivo tool to identify endogenous genes that are either up- or down-regulated by Hox 1.3.