Devinoy Eve, Montoliu Lluís, Baranyi Mária, Thépot Dominique, Hiripi László, Fontaine Marie-Louise, Bodrogi Lilla, Bosze Zsuzsanna
Unité de Génomique et Physiologie de la Lactation, INRA, 78352 Jouy en Josas Cedex, France.
J Dairy Res. 2005;72 Spec No:113-9. doi: 10.1017/s0022029905001111.
For 10 years, the regulatory regions of the mouse and rabbit whey acidic protein gene have been used to express heterologous proteins in the milk of transgenic mice, as well as to produce pharmaceutical proteins, on a large scale, in the milk of transgenic livestock. To date, a broad range of expression levels have been detected, and elucidation of the structure-function relationship in these regulatory regions might help to achieve high levels of expression, reproducibly. An extended 5' regulatory region (17.6 kb v. 6.3 kb) of the rabbit whey acidic promoter resulted in an increased frequency of rabbit whey acidic protein expression in transgenic mice. However, the expression levels were low compared with the high expression levels achieved in both transgenic mice and rabbits using the heterologous kappa-casein in the 6.3 kb rabbit whey acidic protein 5' regulatory region. These results underline the importance of the 3' downstream regulatory regions, which still need to be better characterized in the whey acidic protein gene.
十年来,小鼠和兔乳清酸性蛋白基因的调控区域已被用于在转基因小鼠的乳汁中表达异源蛋白,以及在转基因家畜的乳汁中大规模生产药用蛋白。迄今为止,已检测到广泛的表达水平,阐明这些调控区域中的结构-功能关系可能有助于可重复地实现高水平表达。兔乳清酸性启动子的一个扩展的5'调控区域(17.6 kb对6.3 kb)导致转基因小鼠中兔乳清酸性蛋白表达频率增加。然而,与使用6.3 kb兔乳清酸性蛋白5'调控区域中的异源κ-酪蛋白在转基因小鼠和兔中实现的高表达水平相比,其表达水平较低。这些结果强调了3'下游调控区域的重要性,其在乳清酸性蛋白基因中仍需要更好地表征。