Fukuchi K, Ho L, Younkin S G, Kunkel D D, Ogburn C E, LeBoeuf R C, Furlong C E, Deeb S S, Nochlin D, Wegiel J, Wisniewski H M, Martin G M
Department of Pathology, University of Washington, Seattle, Washington, USA.
Am J Pathol. 1996 Jul;149(1):219-27.
We have established transgenic mice that constitutively overproduce the signal sequence and the 99-amino-acid carboxyl-terminal region of the human beta-amyloid precursor protein. The transgenic mice strongly expressed the transgene in multiple tissues under the control of a cytomegalovirus enhancer/chick beta-actin promoter. There were exceptionally high levels of beta-amyloid peptides in the plasma (approximately 17 times or more compared with the human plasma level). Although some transgenic mice from one founder line developed amyloidosis in the intestine, no neuropathology was found in transgenic mice up to age 29 months. Given the absence of cerebral beta-amyloidosis despite extremely high levels of circulating beta-amyloid peptides in the transgenic mice, the results suggest that local cerebral metabolism of beta-amyloid precursor protein may play a predominant role in cerebral beta-amyloidosis in transgenic mice. Such transgenic mice may be useful for the investigation of the etiology of the disease and for the establishment of therapeutic strategies.
我们已经建立了转基因小鼠，其组成性地过量产生人β-淀粉样前体蛋白的信号序列和99个氨基酸的羧基末端区域。转基因小鼠在巨细胞病毒增强子/鸡β-肌动蛋白启动子的控制下在多个组织中强烈表达转基因。血浆中β-淀粉样肽水平异常高（与人血浆水平相比约为17倍或更高）。尽管来自一个奠基系的一些转基因小鼠在肠道中发生了淀粉样变性，但在29月龄以下的转基因小鼠中未发现神经病理学改变。鉴于转基因小鼠中循环β-淀粉样肽水平极高，但脑内却没有β-淀粉样变性，结果表明β-淀粉样前体蛋白的局部脑代谢可能在转基因小鼠的脑β-淀粉样变性中起主要作用。这种转基因小鼠可能有助于研究该疾病的病因并建立治疗策略。
