MAZZOCCO, Claire; GENEVOIS, Coralie; LI, Qin; DOUDNIKOFF, Evelyne; DUTHEIL, Nathalie; LESTE-LASSERRE, Thierry; AROTCARENA, Marie-Laure; BEZARD, Erwan

doi:10.1038/s41598-024-60613-6

Institut des Maladies Neurodégénératives [Bordeaux] [IMN]

GENEVOIS, Coralie
TBM-Core [Bordeaux] [UMS3427 - INSERM US005]

LI, Qin

Langue

Article de revue

Ce document a été publié dans

Scientific Reports. 2024-04-27, vol. 14, n° 1

Résumé en anglais

Among the several animal models of α-synucleinopathies, the well-known viral vector-mediated delivery of wild-type or mutated (A53T) α-synuclein requires new tools to increase the lesion in mice and follow up in vivo expression. To this end, we developed a bioluminescent expression reporter of the human A53T-α-synuclein gene using the NanoLuc system into an AAV2/9, embedded or not in a fibroin solution to stabilise its expression in space and time. We first verified the expression of the fused protein in vitro on transfected cells by bioluminescence and Western blotting. Next, two groups of C57Bl6Jr mice were unilaterally injected with the AAV-NanoLuc-human-A53T-α-synuclein above the substantia nigra combined (or not) with fibroin. We first show that the in vivo cerebral bioluminescence signal was more intense in the presence of fibroin. Using immunohistochemistry, we find that the human-A53T-α-synuclein protein is more restricted to the ipsilateral side with an overall greater magnitude of the lesion when fibroin was added. However, we also detected a bioluminescence signal in peripheral organs in both conditions, confirmed by the presence of viral DNA corresponding to the injected AAV in the liver using qPCR. © The Author(s) 2024.< Réduire

Mots clés en anglais

Humans

Male

Animals

Mice

Genetics

Procedures

Metabolism

Alpha-Synuclein

C57bl Mouse

Inbred C57bl

Central Nervous System

Dependoparvovirus

Dependovirus

Fibroins

Genetic Vectors

Luciferases

Luminescence

Luminescent Measurements

URI

https://oskar-bordeaux.fr/handle/20.500.12278/206737

DOI

http://dx.doi.org/10.1038/s41598-024-60613-6

Projet Européen

Horizon Europe research and innovation programme
Program Initiative d’Excellence

Project ANR

Translational Research and Advanced Imaging Laboratory - ANR-10-LABX-0057
France Life Imaging - ANR-11-INBS-0006

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In vivo bioluminescence imaging of the intracerebral fibroin-controlled AAV-α-synuclein diffusion for monitoring the central nervous system and peripheral expression

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Résumé en anglais

Mots clés en anglais

URI

DOI

Projet Européen

Project ANR

Unités de recherche

Voir/Ouvrir

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Licence d’utilisation du document

In vivo bioluminescence imaging of the intracerebral fibroin-controlled AAV-α-synuclein diffusion for monitoring the central nervous system and peripheral expression

Langue

Ce document a été publié dans

Résumé en anglais

Mots clés en anglais

URI

DOI

Projet Européen

Project ANR

Unités de recherche