Dissecting pathophysiology of a human dominantly inherited disease, familial amyloidotic polyneuropathy, by using genetically engineered mice
Dissecting pathophysiology of a human dominantly inherited disease, familial amyloidotic polyneuropathy, by using genetically engineered mice
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DOI：
10.2478/fzm-2022-0009
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发表时间：
2022-05
期刊：
影响因子：
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通讯作者：
Zhenghua Li;K. Yamamura
中科院分区：
文献类型：
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作者：
Zhenghua Li;K. Yamamura
家族性淀粉样多神经病（FAP）是一种以周围神经和自主神经病变为特征的系统性淀粉样变性。虽然FAP是由TTR基因点突变引起的典型常染色体显性遗传疾病，但不同国家的平均发病年龄差异很大。这种差异清楚地表明，内在因素和外在（环境）因素的组合塑造了FAP的发展。然而，这些因素很难在人体中进行分析，因为详细的病理组织分析只能在尸检时进行。因此，小鼠模型已经产生并用于解开这些因素。本文综述了迄今为止产生的小鼠模型，以及这些模型如何应用于分析疾病发展中涉及的内在和外在因素以及测试药物疗效。
Abstract Familial amyloidotic polyneuropathy (FAP) is a type of systemic amyloidosis characterized by peripheral and autonomic neuropathy. Although FAP is a typical autosomal dominant disorder caused by a point mutation in the TTR gene, the average age at onset varies significantly among different countries. This discrepancy clearly suggests that a combination of intrinsic factors as well as extrinsic (environmental) factors shapes the development of FAP. However, these factors are difficult to analyze in humans, because detailed pathologic tissue analysis is only possible at autopsy. Thus, mouse models have been produced and used to disentangle these factors. This review covers the mouse models produced thus far and how these models are applied to analyze intrinsic and extrinsic factors involved in disease development and to test drug efficacy.