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.