Engineering transgenes for use in the mammary gland.

Abstract

Our original interest in the milk protein genes stems from studies of Yale Topper and his colleagues performed almost thirty years ago in which casein expression in mammary expiant cultures was employed as a model system for understanding how peptide and steroid hormones regulate milk protein gene expression (1). Once the milk protein cDNAs and genes were cloned in the early 80s (2–4), we were confronted with the question, “What is the appropriate biological model in which to study milk protein gene regulation?” Most of the available breast tumor cell lines, even those that retain hormone receptors, do not express the milk protein genes, and transfection studies with these cells are not particularly informative. Primary mammary epithelial and expiant cultures are also highly variable and difficult to transfect. Fortunately, the development of transgenic mice as a basic research tool provides an ideal model in which to study the hormonal and developmental regulation of milk protein gene expression. Transgenic mice are especially valuable for the analysis of complex systems such as mammary gland where no single cell line can mimic the complete spectrum of developmental, hormonal, cell-substratum, and epithelial-stromal interactions. In 1984 studies were begun to identify the cis-acting sequences required to elicit the appropriate tissue-specific and hormonal regulation of milk protein gene expression in transgenic mice (5). These studies focus on two rat milk protein genes encoding ß-casein and the most abundant rodent whey protein, whey acidic protein (3,4).KeywordsTransgenic MouseMammary GlandMouse Mammary Tumor VirusMammary Gland DevelopmentWhey Acidic ProteinThese 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.