New Developments in Genetic rat models of Parkinson's Disease.
New Developments in Genetic rat models of Parkinson's Disease.
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DOI：
10.1002/mds.27296
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Goldberg MS
中科院分区：
文献类型：
--
作者：
Creed RB;Goldberg MS
帕金森病（PD）的临床前研究在很大程度上依赖于小鼠和大鼠动物模型。最初，PD动物模型主要由化学神经毒素产生，其诱导黑质中多巴胺能神经元的急性损失。在发现与PD有因果关系的基因突变后，小鼠比大鼠更多地用于产生携带PD相关突变的实验室动物，因为大鼠的突变更困难。哺乳动物基因组工程和病毒表达载体优化技术的最新进展增加了PD遗传大鼠模型的使用。新兴的研究工具包括“敲除”大鼠，其中突变与PD有因果关系，包括LRRK 2，α-突触核蛋白，Parkin，PINK 1和DJ-1。大鼠也越来越多地用于转基因和病毒介导的PD相关基因的过表达，特别是α-突触核蛋白。要获得一个单一的动物模型来完全再现像PD这样复杂的人类疾病的每一个特征可能是不现实的。然而，与具有相同突变的小鼠相比，许多PD的遗传大鼠动物模型更好地再现了PD的关键方面，包括黑质中多巴胺能神经元的进行性丧失、运动行为缺陷和异常α-突触核蛋白蛋白聚集体的年龄依赖性形成。在这里，我们简要地回顾了遗传大鼠模型的PD，可能有更大的潜力，以确定潜在的机制，发现新的治疗靶点，并开发急需的治疗方法，以减缓或停止疾病的进展。
Preclinical research on Parkinson’s disease (PD) has relied heavily on mouse and rat animal models. Initially, PD animal models were generated primarily by chemical neurotoxins that induce acute loss of dopaminergic neurons in the substantia nigra. Upon the discovery of genetic mutations causally linked to PD, mice were used more than rats to generate laboratory animals bearing PD-linked mutations because mutagenesis was more difficult in rats. Recent advances in technology for mammalian genome engineering and optimization of viral expression vectors have increased the use of genetic rat models of PD. Emerging research tools include “knockout” rats with disruption of genes in which mutations have been causally linked to PD, including LRRK2, α-synuclein, Parkin, PINK1 and DJ-1. Rats have also been increasingly used for transgenic and viral-mediated overexpression of genes relevant to PD, particularly α-synuclein. It may not be realistic to obtain a single animal model that completely reproduces every feature of a human disease as complex as PD. Nevertheless, compared to mice with the same mutations, many genetic rat animal models of PD better reproduce key aspects of PD including progressive loss of dopaminergic neurons in the substantia nigra, locomotor behavior deficits, and age-dependent formation of abnormal α-synuclein protein aggregates. Here we briefly review new developments in genetic rat models of PD that may have greater potential for identifying underlying mechanisms, for discovering novel therapeutic targets, and for developing greatly needed treatments to slow or halt disease progression.
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DOI：
10.1073/pnas.1512876113
发表时间：
2016-02-16
影响因子：
11.1
作者：
Fares, Mohamed-Bilal;Maco, Bohumil;Lashuel, Hilal A.
通讯作者：
Lashuel, Hilal A.
影响因子：
5.3
作者：
Decressac, M.;Mattsson, B.;Bjorklund, A.
通讯作者：
Bjorklund, A.
影响因子：
5.3
作者：
Caudal, D.;Alvarsson, A.;Svenningsson, P.
通讯作者：
Svenningsson, P.
影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
影响因子：
4.8
作者：
Daher, Joao P. L.;Abdelmotilib, Hisham A.;West, Andrew B.
通讯作者：
West, Andrew B.