Many 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 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 previously cloned, sequenced, and studied the expression of one of the murine Antennapedia class genes known as Hox 1.3. To test Hox 1.3 in vivo biofunction, we have generated conditional gain of function 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 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 nontransgenic pregnant mice also induces transgene activity in embryos. As assayed by in situ hybridization, the tissue distribution of induced transgene expression in embryos paralleled that seen in adults. Our primary goal is to use this in vivo tool to identify endogenous genes that are either up- or down-regulated by Hox 1.3.
