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.
Rosen
J M
JM
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030-3498, U.S.A.
Li
S
S
Raught
B
B
Hadsell
D
D
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002364:Caseins / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008894:Milk Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D019076:Transgenes / Q000235:genetics*
D002364:Caseins; D008894:Milk Proteins; D012333:RNA, Messenger; C024471:whey acidic proteins; D007334:Insulin-Like Growth Factor I; D004247:DNA