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Life Technologies
™
| lifetechnologies.com/parkinsons
"Dr. Birgitt Schuele, ISSCR 2013—
Generating Parkinson's disease models"
(18:20)
Watch the ISSCR 2013 presentation
by Dr. Birgitt Schuele of The
Parkinson's Institute.
contribution of α-synuclein deposits to PD-relevant phenotypes
seen in cells derived from these iPSC lines.
Next, to understand the impacts of the LRRK2 G2019S and
GBA N370S mutations, we studied an iPSC line harboring
both mutations, generated from a 61-year-old male donor
with severe PD symptoms, and corrected each mutation back
to wild type. LRRK2 (leucine-rich repeat kinase 2) is a large
multi-domain protein that contains protein-protein interaction
domains flanking a catalytic core that harbors a GTPase and
a kinase domain. Although the exact role of the LRRK2 gene
in Parkinson's disease is unknown, several mutations in
LRRK2 have been linked to PD, with G2019S being the most
common one [4]. The GBA gene codes for glucocerebrosidase,
which is involved in normal lysosomal function. Mutations
in the GBA gene, such as N370S, greatly reduce or eliminate
glucocerebrosidase enzyme activity, and cause toxic levels of
glucocerebroside and related substances to build up within
cells. This can lead to tissue and organ damage. Mutations in
GBA are associated with Parkinson's disease, increasing
the probability of developing the disease by five-fold [5].
Using GeneArt
®
Precision TALs technology, heterozygous
mutations in the LRRK2 and GBA genes were edited back to
homozygous wild type via homology-directed repair (HDR).
Cells differentiated from the resulting parental and edited iPSC
lines will be used in future phenotypic studies.
http://www.youtube.com
watch?v=pJiMCwQ1Ad4
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