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Presenilin-deficient multipotent cell lines and screening methods for intramembrane-regulated proteolytic activities using these lines
Presenilin-deficient multipotent cell lines and screening methods for intramembrane-regulated proteolytic activities using these lines
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机译:早老素缺乏的多能细胞系和使用这些细胞系的膜内调节蛋白水解活性的筛选方法
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摘要
The present invention relates to the field of neurological and physiological dysfunctions associated with Alzheimers disease, more particularly to mutant embryonic stem (ES) cell lines characterized by no detectable -secretase activity, derived from double presenilin (PS 1 and PS 2) knockout mice embryos. These cell lines can be used for in vitro screening of molecules and products involved in regulated intramembrane proteolysis of proteins such as the PP, the APP-like proteins, Notch, Ire-1p, and other integral membrane proteins to identify proteases responsible for the latter proteolysis, like gamma-secretases, or proteins involved in the control of these proteolytic activities. These mutant ES cell lines can be manipulated to differentiate into fibroblasts, neurons, or myocytes or can be used to generate novel transgenic mice. Moreover, a reporter system comprising a chimeric molecule to detect the above-mentioned intramembrane proteolysis or modulators thereof has been developed.
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