Rosen J M, Li S, Raught B, Hadsell D
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030-3498, U.S.A.
Am J Clin Nutr. 1996 Apr;63(4):627S-32S. doi: 10.1093/ajcn/63.4.627.
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.
已确定了大鼠β-酪蛋白和乳腺中乳清酸性蛋白（WAP）基因的激素调节及组织特异性表达所需的特定调控区域。已鉴定出具有多个转录因子结合位点的复合反应元件。乳腺特异性基因表达似乎不是由单一转录因子介导的，而是需要几种因子之间的协同相互作用。催乳激素调节的信号转导途径导致转录因子在这些元件内结合和相互作用、染色质结构变化以及乳蛋白基因表达。β-酪蛋白和WAP mRNA的5'和3'非翻译区内的基因内序列分别对于这些基因的有效表达似乎也至关重要。可以设计将异源基因（如胰岛素样生长因子I）的表达靶向乳腺的载体。该技术可用于操纵转基因动物的乳汁成分，一个成果是改进婴儿配方奶粉。
