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从一名携带PRKN基因复合杂合突变的男性帕金森病患者中生成诱导多能干细胞系FINi002-A。

Generation of the iPSC line FINi002-A from a male Parkinson's disease patient carrying compound heterozygous mutations in the PRKN gene.

作者信息

Pavan C, Jin J, Jong S, Strbenac D, Davis R L, Sue C M, Johnston J, Lynch T, Halliday G, Kirik D, Parish C L, Thompson L H, Ovchinnikov D A

机构信息

The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne VIC 3010 Australia.

University of Sydney, Sydney, NSW 2006, Australia.

出版信息

Stem Cell Res. 2023 Dec;73:103211. doi: 10.1016/j.scr.2023.103211. Epub 2023 Oct 17.

Abstract

The most common cause of autosomal recessive familial Parkinson's disease (PD) are mutations in the PRKN/PARK2 gene encoding an E3 ubiquitin protein-ligase PARKIN. We report the generation of an iPSC cell line from the fibroblasts of a male PD patient carrying a common missense variant in exon 7 (p.Arg275Trp), and a 133 kb deletion encompassing exon 8, using transiently-present Sendai virus. The established line displays typical human primed iPSC morphology and expression of pluripotency-associated markers, normal karyotype without SNP array-detectable copy number variations and can give rise to derivatives of all three embryonic germ layers. We envisage the usefulness of this iPSC line, carrying a common and well-studied missense mutation in the RING1 domain of the PARKIN protein, for the elucidation of PARKIN-dependent mechanisms of PD using in vitro and in vivo models.

摘要

常染色体隐性遗传性帕金森病(PD)最常见的病因是编码E3泛素蛋白连接酶帕金(PARKIN)的PRKN/PARK2基因突变。我们报告了使用瞬时存在的仙台病毒,从一名男性PD患者的成纤维细胞中生成诱导多能干细胞(iPSC)系,该患者在第7外显子携带常见错义变体(p.Arg275Trp),并存在一个包含第8外显子的133 kb缺失。所建立的细胞系表现出典型的人类始发态iPSC形态和多能性相关标志物的表达,核型正常,无单核苷酸多态性阵列可检测到的拷贝数变异,并且能够分化产生所有三个胚胎胚层的衍生物。我们设想,这种在帕金蛋白RING结构域携带常见且经过充分研究的错义突变的iPSC系,对于利用体外和体内模型阐明PD的帕金依赖性机制具有重要作用。

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