Meade H, Gates L, Lacy E, Lonberg N
Biogen Inc., Cambridge, MA 02142.
Biotechnology (N Y). 1990 May;8(5):443-6. doi: 10.1038/nbt0590-443.
We have produced a line of transgenic mice carrying a hybrid bovine alpha S1 casein/human urokinase gene. Bovine alpha S1-casein gene regulatory sequences specifically direct expression of the human urokinase gene in lactating mammary tissue from these mice. Urokinase is a 54 kD protein with 9 disulfide bonds that is normally synthesized in the kidney; however, the casein/urokinase transgenic mice secrete active human urokinase into their milk at concentrations of 1-2 mg/ml. The mice show no other abnormalities. They give birth to, and nurse, normal sized healthy litters. Thus it is possible to produce high concentrations of a large, cysteine rich, non-milk protein in the milk of transgenic animals. This line of transgenic mice provides a model for the eventual production of transgenic farm animals producing high levels of recombinant proteins in their milk.
我们培育出了一系列携带杂交牛αS1酪蛋白/人尿激酶基因的转基因小鼠。牛αS1-酪蛋白基因调控序列特异性地指导人尿激酶基因在这些小鼠的泌乳乳腺组织中表达。尿激酶是一种具有9个二硫键的54kD蛋白质，通常在肾脏中合成；然而，酪蛋白/尿激酶转基因小鼠以1-2mg/ml的浓度将活性人尿激酶分泌到它们的乳汁中。这些小鼠没有表现出其他异常。它们能生育并哺育正常大小的健康幼崽。因此，有可能在转基因动物的乳汁中产生高浓度的一种大的、富含半胱氨酸的非乳蛋白。这一系列转基因小鼠为最终培育出能在乳汁中高水平表达重组蛋白的转基因农场动物提供了一个模型。
