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BACward 一瞥神经退行性变:LRRK2、SNCA 和 MAPT BAC 转基因小鼠的疾病分子见解。

A BACwards glance at neurodegeneration: molecular insights into disease from LRRK2, SNCA and MAPT BAC-transgenic mice.

机构信息

Department of Physiology, Anatomy and Genetics and Oxford Parkinson's Disease Centre, University of Oxford, Le Gros Clark Building, South Parks Road, Oxford OX1 3QX, UK.

出版信息

Biochem Soc Trans. 2011 Aug;39(4):862-7. doi: 10.1042/BST0390862.

DOI:10.1042/BST0390862
PMID:21787314
Abstract

BAC (bacterial artificial chromosome)-transgenic mice expressing a transgene from an entire genomic locus under the control of the native promoter offer the opportunity to generate more accurate genetic models of human disease. The present review discusses results of recent studies investigating PD (Parkinson's disease) and tauopathies using BAC-transgenic mice carrying either the LRRK2 (leucine-rich repeat kinase 2), α-synuclein (SNCA) or MAPT (microtubule-associated protein tau) genes. In all lines, expression of the WT (wild-type) gene resulted in physiologically relevant protein expression. The effect of expressing the mutant form of a gene varied depending on the mouse strain or the particular disease mutation used, although it was common to see either neurochemical or behavioural differences in these animals. Overall, BAC technology offers an exciting opportunity to generate a wide range of new animal models of human-disease states.

摘要

BAC(细菌人工染色体)-转基因小鼠在天然启动子的控制下表达来自整个基因组基因座的转基因,为生成更准确的人类疾病遗传模型提供了机会。本综述讨论了使用携带 LRRK2(富含亮氨酸重复激酶 2)、α-突触核蛋白(SNCA)或 MAPT(微管相关蛋白 tau)基因的 BAC 转基因小鼠研究 PD(帕金森病)和 tau 病的最新研究结果。在所有品系中,WT(野生型)基因的表达导致了生理相关的蛋白质表达。表达基因突变体的效果因小鼠品系或使用的特定疾病突变而异,尽管这些动物通常会出现神经化学或行为差异。总的来说,BAC 技术为生成广泛的人类疾病状态的新型动物模型提供了令人兴奋的机会。

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