SYSTEMIC AMYLOIDOSIS IN TRANSGENIC MICE CARRYING THE HUMAN MUTANT TRANSTHYRETIN (MET-30) GENE - PATHOLOGICAL AND IMMUNOHISTOCHEMICAL SIMILARITY TO HUMAN FAMILIAL AMYLOIDOTIC POLYNEUROPATHY, TYPE-I
SYSTEMIC AMYLOIDOSIS IN TRANSGENIC MICE CARRYING THE HUMAN MUTANT TRANSTHYRETIN (MET-30) GENE - PATHOLOGICAL AND IMMUNOHISTOCHEMICAL SIMILARITY TO HUMAN FAMILIAL AMYLOIDOTIC POLYNEUROPATHY, TYPE-I
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DOI：
10.1007/bf02778004
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发表时间：
1994-02-01
影响因子：
5.1
通讯作者：
YAMARNURA, K
中科院分区：
文献类型：
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作者：
ARAKI, S;YI, S;YAMARNURA, K
为了分析I型家族性淀粉样多发性神经病（FAP）中淀粉样蛋白沉积的病理过程，通过引入人突变型甲状腺素运载蛋白（TTR）基因（MT-hMet 30）使小鼠转基因。选用近交系小鼠C57 BL/6。转基因小鼠在出生后24个月内每隔3个月用乙醚麻醉处死。在这些转基因小鼠中，淀粉样蛋白沉积开始于胃肠道，心血管系统和肾脏，并随着年龄的增长扩展到各种其他器官和组织。淀粉样蛋白沉积的模式是类似的，在人类FAP尸检病例中观察到的，除了它的情况下，在脉络丛和周围和自主神经system.We提取的淀粉样蛋白原纤维从这些小鼠的肾脏与人类突变TTR基因和免疫化学和电子显微镜分析。沉积的淀粉样蛋白由人突变TTR和小鼠血清淀粉样蛋白P成分组成。转基因小鼠的淀粉样原纤维在形态学和免疫化学上与人FAP相似，最显著的病理特征是外周和自主神经组织中无淀粉样沉积。因此，其他内在因素可能参与了人FAP神经组织中淀粉样蛋白的沉积。
To analyze the pathologic processes of amyloid deposition in type I familial amyloidotic polyneuropathy (FAP), mice were made transgenic by introducing the human mutant transthyretin (TTR) gene(MT-hMet 30). An inbred strain of mouse, C57 BL/6, was chosen. Transgenic mice were killed using ether anesthesia at 3-mo intervals up to 24 mo after birth. In these transgenic mice, amyloid deposition started in the gastrointestinal tract, cardiovascular system, and kidneys and extended to various other organs and tissues with advancing age. The pattern of amyloid deposition was similar to that observed in human autopsy cases of FAP, except for its absence in the choroid plexus and in the peripheral and autonomic nervous systems.We extracted the amyloid fibrils from kidneys of these mice with a human mutant TTR gene and analyzed them immunochemically and electronmicroscopically. Deposited amyloid was shown to be composed of human mutant TTR and mouse serum amyloid P component. Amyloid fibril from transgenic mice was morphologically and immunohistochemically similar to that of human FAP.The most striking pathologic feature of the transgenic mice was the absence of amyloid deposition in the peripheral and autonomic nervous tissues. Thus, other intrinsic factors may be involved in amyloid deposition in the nervous tissues of human FAP.