Expression of full-length human pro-urokinase in mammary glands of transgenic mice
| Autor: | Alex Deikin, Andrey Popov, I. L. Goldman, Alexsander Shevelev, Alex Krasnov, E. R. Sadchikova, Sergey V. Razin, Lilia Verbovaya, Yaroslav Gursky, Nicolai Rutkevich, Robert Bibilashvili, Sofia G. Georgieva, Mikchail Minashkin, T G Ermolkevich |
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| Rok vydání: | 2008 |
| Předmět: |
Genetically modified mouse
Proteases medicine.medical_treatment Transgene Mammary gland Mice Transgenic Mice Mammary Glands Animal Genetics medicine Animals Humans Serine protease Enzyme Precursors Protease biology Escherichia coli Proteins Molecular biology Urokinase-Type Plasminogen Activator Recombinant Proteins Enzyme Activation medicine.anatomical_structure biology.protein Animal Science and Zoology Female Ecotin Periplasmic Proteins Agronomy and Crop Science Plasminogen activator Biotechnology |
| Zdroj: | Transgenic research. 18(5) |
| ISSN: | 1573-9368 |
| Popis: | Human pro-urokinase expressed in the mammary glands of transgenic animals is quickly activated and converted to urokinase by proteases that are present in the milk. Thus, it is nearly impossible to isolate full-sized pro-urokinase from the milk of transgenic animals. To solve this problem, we constructed transgenic mice that express human pro-urokinase and modified ecotin, which is a potent serine protease inhibitor from E. coli, in their mammary glands. The gene encoding ecotin was modified so as to enhance its specificity for the human urokinase-type plasminogen activator. Co-expression of modified ecotin and human pro-urokinase in the mammary glands allows for purification of full-length human pro-urokinase from these transgenic mice. The results described here suggest a general way of preventing the activation of zymogens that are expressed in the mammary glands of transgenic animals by co-expression of a zymogen along with a protease inhibitor. |
| Databáze: | OpenAIRE |
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