CRISPR/Cas9-mediated PINK1 deletion leads to neurodegeneration in rhesus monkeys

摘要：

Dear Editor,PINK1 mutations cause autosomal recessive and early-onset Parkinson”s disease (PD) with selective neurodegeneration.Unfortunately,current PINK1 knockout (KO) mouse1,2 and pig models3,4 are unable to recapitulate the selective and overt neurodegeneration seen in PD patients.Furthermore,endogenous Pink1 in the mouse brain is expressed at very low levels and can only be detected via immunoprecipitation,5 meaning that PINK1”s function in the mammalian brain needs to be assessed using larger animals that are closer to humans.We previously used CRISPR/Cas9 to target the monkey gene in one-cell stage embryos.6 Using the same approach,we designed two gRNAs to target exon 2 (T1) and exon 4 (T2),which encode a kinase domain in the PINK1 gene of rhesus monkeys (Fig.1a).CRISPR/Cas9 and PINK1 gRNAs were injected into one-cell stage rhesus monkey embryos.

所属期刊栏目：29

资助基金：the National Key Research and Development Program of China Stem Cell and Translational Research2017YFA0105102,2017YFA0105201;the State Key Laboratory of Molecular Developmental Biology,China.We thank Yi Hong for electron microscopic examination;Jinquan Gao,Qiang Sun,Haiquan Shang,Hua Zhu,Mu Liu,Tao Zhu and Ling Zhang for animal care and behavioral analysis;Baogui Zhang,Ming Song and Yanyan Liu for MRI image acquisition;Shang-Hsun Yang for technical advice;Giovanni Coppola,Zhaohui Qin and Luxiao Chen for large deletion and off-target analysis of the whole genome sequence;the Chinese Academy of Sciences-Institute of Automation Center for Advanced Imaging for MRI experiments and data analysis.We thank Cheryl Strauss for editing the manuscript

在线出版日期：2019-05-21（万方平台首次上网日期，不代表论文的发表时间）

页数：共3页

页码：334-336