Mice Expressing A53T/A30P Mutant Alpha-Synuclein in Dopamine Neurons Do Not Display Behavioral Deficits

Cameron Keomanivong; Josephine Schamp; Ervina Tabakovic; Ramasamy Thangavel; Georgina Aldridge; Andrew A Pieper; Nandakumar S Narayanan

doi:10.1523/ENEURO.0170-23.2023

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Mice Expressing A53T/A30P Mutant Alpha-Synuclein in Dopamine Neurons Do Not Display Behavioral Deficits

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Mice Expressing A53T/A30P Mutant Alpha-Synuclein in Dopamine Neurons Do Not Display Behavioral Deficits

Cameron Keomanivong, Josephine Schamp, Ervina Tabakovic, Ramasamy Thangavel, Georgina Aldridge, Andrew A Pieper and Nandakumar S Narayanan

eNeuro, Vol.11(2), pp.1-6

02/2024

DOI: 10.1523/ENEURO.0170-23.2023

PMCID: PMC10866330

PMID: 38351057

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https://doi.org/10.1523/ENEURO.0170-23.2023View

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Abstract

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.

alpha-Synuclein - genetics

alpha-Synuclein - metabolism

Animals

Disease Models, Animal

Dopaminergic Neurons - metabolism

Mice

Mice, Transgenic

Parkinson Disease - genetics

Tyrosine 3-Monooxygenase - genetics

Details

Title: Subtitle: Mice Expressing A53T/A30P Mutant Alpha-Synuclein in Dopamine Neurons Do Not Display Behavioral Deficits
Creators: Cameron Keomanivong - University of Iowa
Josephine Schamp - York University
Ervina Tabakovic - University of Iowa
Ramasamy Thangavel - University of Iowa
Georgina Aldridge - University of Iowa
Andrew A Pieper - University Hospitals Cleveland Medical Center
Nandakumar S Narayanan - University of Iowa
Resource Type: Journal article
Publication Details: eNeuro, Vol.11(2), pp.1-6
DOI: 10.1523/ENEURO.0170-23.2023
PMID: 38351057
PMCID: PMC10866330
NLM abbreviation: eNeuro
eISSN: 2373-2822
Grant note: name: Titan Neurological Fund
Language: English
Date published: 02/2024
Academic Unit: Neurology; Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984559929402771

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