Titre :

Functional characterization of a fus mutant zebrafish line as a novel genetic model for als

Auteur(s) :

Bourefis, Annis-Rayan [Auteur]
Campanari, Maria-Letizia [Auteur]
Buee-Scherrer, Valerie [Auteur]
Kabashi, Edor [Auteur]

Titre de la revue :

Neurobiology of Disease

Nom court de la revue :

Neurobiol. Dis.

Pagination :

104935

Date de publication :

2020-05-04

ISSN :

1095-953X

Mot(s)-clé(s) :

Tau Frontotemporal dementia
FUS
Amyotrophic lateral sclerosis (ALS)
Zebrafish
Neuromuscular junction
Motor neuron
Genetics
Neurodegeneration

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Mutations in Fused in sarcoma (FUS), an RNA-binding protein, are known to cause Amyotrophic Lateral Sclerosis (ALS). However, molecular mechanisms due to loss of FUS function remain unclear and controversial. Here, we ...
Lire la suite >Mutations in Fused in sarcoma (FUS), an RNA-binding protein, are known to cause Amyotrophic Lateral Sclerosis (ALS). However, molecular mechanisms due to loss of FUS function remain unclear and controversial. Here, we report the characterization and phenotypic analysis of a deletion mutant of the unique FUS orthologue in zebrafish where Fus protein levels are depleted. The homozygous mutants displayed a reduced lifespan as well as impaired motor abilities associated with specific cellular deficits, including decreased motor neurons length and neuromuscular junctions (NMJ) fragmentation. Furthermore, we demonstrate that these cellular impairments are linked to the misregulation of mRNA expression of acetylcholine receptor (AChR) subunits and histone deacetylase 4, markers of denervation and reinnervation processes observed in ALS patients. In addition, fus loss of function alters tau transcripts favoring the expression of small tau isoforms. Overall, this new animal model extends our knowledge on FUS and supports the relevance of FUS loss of function in ALS physiopathology.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Équipe(s) de recherche :

Alzheimer et Tauopathies

Date de dépôt :

2021-06-23T13:47:12Z