The mammary gland as a bioreactor: factors regulating the efficient expression of milk protein-based transgenes.

Specific regulatory regions required for hormonal regulation and tissue-specific expression of rat beta-casein and why acidic protein (WAP) genes in the mammary gland have been defined. Composite response elements with multiple binding sites for several transcription factors have been identified. Mammary gland-specific gene expression appears not to be mediated by a single transcription factor, but instead requires cooperative interactions among several factors. Signal transduction pathways regulated by lactogenic hormones result in transcription factor binding and interaction within these elements, chromatin-structure changes, and milk-protein gene expression. Intragenic sequences in the 5' and 3' untranslated regions of the beta-casein and WAP mRNAs, respectively, also appear crucial for the efficient expression of these genes. Vectors to target the expression of heterologous genes, such as insulin-like growth factor I, to the mammary gland can be designed. This technology can be used to manipulate milk composition in transgenic animals, one result being improved infant formulas.