Diverse genetic regulatory elements are required to direct the proper tissue-specific and developmental expression of the murine adenosine deaminase gene.

Abstract

Development of an organism from a single cell to a multitude of diverse cell types requires the differential expression and repression of 75% of the genome and the ubiquitous expression of the remaining 25%. As an initial step in defining the biochemical mechanisms governing differential gene expression, we wish to define the cis-acting regulatory sequences involved. The enzymes of purine and pyrimidine metabolism offer the opportunity to investigate both the mechanisms of ubiquitious and tissue-specific gene expression. Most of these genes are expressed at low levels in most cell types and the expression of some are significantly upregulated in a tissue-specific and developmentally regulated manner. An excellent example of this pattern of expression is the murine adenosine deaminase (ADA) gene. Expressed in every tissue of the mouse, ADA expression is more than 100-fold higher in tissues at the fetal-maternal interface (decidua and placenta), the keratinizing epithelium of the upper gastrointestinal tract and the absorptive epithelium of the duodenum (1). Two phases of enhanced ADA expression occur at the fetal/maternal interface (2). From day 6 to 9 of gestation, high levels of ADA are found in maternal decidual cells. From day 9 through birth high levels of ADA are found in fetally derived cells primarily in the basal zone of the placenta. Following birth, ADA levels increase in the gastrointestinal epithelium (1).KeywordsHypersensitive SitePyrimidine MetabolismGenetic Regulatory ElementThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.