deletion of the wd40 domain of lrrk2 in zebrafish causes parkinsonism-like loss of neurons and locomotive defect斑马鱼体内基因lrrk2的删除wd40域导致parkinsonism-like神经元和机车缺陷的损失.pdfVIP

Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect 1 1 1 1 2 Donglai Sheng , Dianbo Qu , Ken Hon Hung Kwok , Seok Shin Ng , Adrian Yin Ming Lim , Sharon Siqi 1 3 3 4 2 5,6 Aw , Charlie Wah Heng Lee , Wing Kin Sung , Eng King Tan , Thomas Lufkin , Suresh Jesuthasan , 2 1 Mathavan Sinnakaruppan , Jianjun Liu * 1 Department of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore, Singapore, 2 Department of Stem Cell and Developmental Biology, Genome Institute of Singapore, A*STAR, Singapore, Singapore, 3 Department of Computational and Mathematical Biology, Genome Institute of Singapore, A*STAR, Singapore, Singapore, 4 National Neuroscience Institute and Duke–NUS Graduate Medical School, Singapore, Singapore, 5 Neuroscience Research Partnership, A*STAR, Singapore, Singapore, 6 Department of Physiology, National University of Singapore, Singapore, Singapore Abstract LRRK2 plays an important role in Parkinson’s disease (PD), but its biological functions are largely unknown. Here, we cloned the homolog of human LRRK2, characterized its expression, and investigated its biological functions in zebrafish. The blockage of zebrafish LRRK2 (zLRRK2) protein by morpholinos caused embryonic lethality and severe developmental defects such as growth retardation and loss of neurons. In contrast, the deletion of the WD40 domain of zLRRK2 by morpholinos targeting splicing did not induce severe embryonic developmental defects; rather it ca