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In Vitro CRISPR/Cas9-Directed Gene Editing to Model LRRK2 G2019S Parkinson’s Disease in Common Marmosets by Vermilyea, Scott C.; Babinski, Alexander; Tran, Nina; To, Samantha; Guthrie, Scott; Kluss, Jillian H.; Schmidt, Jenna Kropp; Wiepz, Gregory J.; Meyer, Michael G.; Murphy, Megan E.; Cookson, Mark R.; Emborg, Marina E.; Golos, Thaddeus G. is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is In Vitro CRISPR/Cas9-Directed Gene Editing to Model LRRK2 G2019S Parkinson’s Disease in Common Marmosets about?

Leucine-rich repeat kinase 2 (LRRK2) G2019S is a relatively common mutation, associated with 1–3% of Parkinson’s disease (PD) cases worldwide. G2019S is hypothesized to increase LRRK2 kinase activity. Dopaminergic neurons derived from induced pluripotent stem cells of PD patients carrying LRRK2 G2019S are reported to have several phenotypes compared to wild type controls, including increased activated caspase-3 and reactive oxygen species (ROS), autophagy dysfunction, and simplification of neurites. The common marmoset is envisioned as a candidate nonhuman primate species for comprehensive modeling of genetic mutations. Here, we report our successful use of CRISPR/Cas9 with repair template-mediated homology directed repair to introduce the LRRK2 G2019S mutation, as well as a truncation of the LRRK2 kinase domain, into marmoset embryonic and induced pluripotent stem cells. We found that, similar to humans, marmoset LRRK2 G2019S resulted in elevated kinase activity. Phenotypic evaluation after dopaminergic differentiation demonstrated LRRK2 G2019S-mediated increased intracellular ROS, decreased neuronal viability, and reduced neurite complexity. Importantly, these phenotypes were not

Who reads In Vitro CRISPR/Cas9-Directed Gene Editing to Model LRRK2 G2019S Parkinson’s Disease in Common Marmosets?

It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.

Author
Vermilyea, Scott C.; Babinski, Alexander; Tran, Nina; To, Samantha; Guthrie, Scott; Kluss, Jillian H.; Schmidt, Jenna Kropp; Wiepz, Gregory J.; Meyer, Michael G.; Murphy, Megan E.; Cookson, Mark R.; Emborg, Marina E.; Golos, Thaddeus G.
Publisher
Springer Science and Business Media LLC; London: Nature Publishing Group; [London]: Springer Nature; Nature Publishing Group; Society for Mining, Metallurgy and Exploration Inc.; Research Square; Springer Nature; Island Press (ISSN 2045-2322)
Published
2020
Language
EN
ISBN
9784159802067
Field
Biochemistry, Genetics and Molecular Biology (Life Sciences)

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