| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
162-334 |
DRI_Background |
denotes |
The p.G2019S mutation of the leucine-rich repeat kinase 2 (LRRK2) has been identified as the most prevalent genetic cause of familial and sporadic Parkinson's disease (PD). |
| T2 |
335-524 |
DRI_Background |
denotes |
The Cre-LoxP recombination system has been used to correct the LRRK2-G2019S mutation in patient derived human induced pluripotent stem cells (hiPSCs) in order to generate isogenic controls. |
| T3 |
525-588 |
DRI_Background |
denotes |
However, the remaining LoxP site can influence gene expression. |
| T4 |
589-633 |
DRI_Approach |
denotes |
In this study, we report the generation of a |
| T5 |
671-740 |
DRI_Approach |
denotes |
hiPS cell line edited with the CRISPR/Cas9 and piggyBac technologies. |
| T6 |
741-926 |
DRI_Outcome |
denotes |
We observed that the percentage of Tyrosine Hydroxylase (TH) positive neurons with a total neurite length of >2000μm was significantly reduced in LRRK2-G2019S dopaminergic (DA) neurons. |
| T7 |
927-999 |
DRI_Outcome |
denotes |
The average branch number in LRRK2-G2019S DA neurons was also decreased. |
| T8 |
1000-1268 |
DRI_Outcome |
denotes |
In addition, we have shown that in vitro TH positive neurons with a total neurite length of >2000μm were positive for Serine 129 phosphorylated (S129P) alpha-Synuclein (αS) and we hypothesize that S129P-αS plays a role in the maintenance or formation of long neurites. |
| T9 |
1269-1284 |
DRI_Approach |
denotes |
In summary, our |
| T10 |
1322-1500 |
DRI_Approach |
denotes |
cell lines allow standardized, genetic background independent, in vitro PD modeling and provide new insights into the role of LRRK2-G2019S and S129P-αS in the pathogenesis of PD. |
