Buxbaum J D, Christensen J L, Ruefli A A, Greengard P, Loring J F
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021.
Biochem Biophys Res Commun. 1993 Dec 15;197(2):639-45. doi: 10.1006/bbrc.1993.2527.
A major component of amyloid deposits found in Alzheimer disease and Down syndrome is the beta/A4 peptide, which is derived from the Alzheimer amyloid protein precursor (APP). Recent evidence indicates that increases in APP expression and/or beta/A4 peptide accumulation may underlie the amyloidosis characteristic of these diseases. In the present study, transgenic mice carrying the entire human APP gene were studied for expression of human APP. Significant expression of human APP protein was observed in these animals, and this expression paralleled the expression of endogenous APP. These results, which represent a first demonstration of significant human APP expression in transgenic animals, support the use of such animals to study human APP expression and processing in vivo and possibly as models for the amyloidosis associated with Alzheimer disease.
在阿尔茨海默病和唐氏综合征中发现的淀粉样沉积物的一个主要成分是β/A4肽,它源自阿尔茨海默淀粉样蛋白前体(APP)。最近的证据表明,APP表达增加和/或β/A4肽积累可能是这些疾病淀粉样变性的基础。在本研究中,对携带整个人类APP基因的转基因小鼠进行了人类APP表达的研究。在这些动物中观察到了人类APP蛋白的显著表达,并且这种表达与内源性APP的表达平行。这些结果首次证明了转基因动物中人类APP的显著表达,支持使用此类动物在体内研究人类APP的表达和加工,并且可能作为与阿尔茨海默病相关的淀粉样变性的模型。