| 摘要 |
The present invention relates to the field of neurological and physiological dysfunctions associated with Alzheimer's disease, more particularly to mutant embryonic stem (ES) cell lines characterized by no detectable gamma-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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