THE MAMMARY-GLAND AS A BIOREACTOR - FACTORS REGULATING THE EFFICIENT EXPRESSION OF MILK PROTEIN-BASED TRANSGENES

Specific regulatory regions required for hormonal regulation and tissu e-specific expression of rat beta-casein and whey acidic protein (WAP) genes in the mammary gland have been defined. Composite response elem ents with multiple binding sites for several transcription factors hav e 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 pa thways regulated by lactogenic hormones result in transcription factor binding and interaction within these elements, chromatin-structure ch anges, and milk-protein gene expression. Intragenic sequences in the 5 ' and 3' untranslated regions of the beta-casein and WAP mRNAs, respec tively, also appear crucial for the efficient expression of these gene s. Vectors to target the expression of heterologous genes, such as ins ulin-like growth factor I, to the mammary gland can be designed. This technology can be used to manipulate milk composition in transgenic an imals, one result being improved infant formulas.