RT Journal Article
SR Electronic
T1 Mice Expressing A53T/A30P Mutant Alpha-Synuclein in Dopamine Neurons Do Not Display Behavioral Deficits
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0170-23.2023
DO 10.1523/ENEURO.0170-23.2023
VO 11
IS 2
A1 Keomanivong, Cameron
A1 Schamp, Josephine
A1 Tabakovic, Ervina
A1 Thangavel, Ramasamy
A1 Aldridge, Georgina
A1 Pieper, Andrew A.
A1 Narayanan, Nandakumar S.
YR 2024
UL http://www.eneuro.org/content/11/2/ENEURO.0170-23.2023.abstract
AB Alpha-synuclein has been implicated in neurodegenerative diseases such as Parkinson's disease and dementia with Lewy bodies, with A53T and A30P mutations shown to be disease causing. It has been reported that hemizygous transgenic mice with tyrosine hydroxylase promotor-driven expression of A53T/A30P mutant alpha-synuclein in dopamine neurons provide a useful preclinical model of these conditions by virtue of developing behavioral deficits. Here, we report a lack of replication of this finding. Despite detecting robust overexpression of A53T/A30P mutant alpha-synuclein in dopamine neurons, we did not observe decreased tyrosine hydroxylase immunofluorescence or behavioral deficits in these mice. Our results demonstrate that preclinical models of synucleinopathy need careful validation in the field.