Spinal muscular atrophy-like phenotype in a mouse model of acid ceramidase deficiency.
Commun Biol
; 6(1): 560, 2023 05 25.
Article
en En
| MEDLINE
| ID: mdl-37231125
ABSTRACT
Mutations in ASAH1 have been linked to two allegedly distinct disorders Farber disease (FD) and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). We have previously reported FD-like phenotypes in mice harboring a single amino acid substitution in acid ceramidase (ACDase), P361R, known to be pathogenic in humans (P361R-Farber). Here we describe a mouse model with an SMA-PME-like phenotype (P361R-SMA). P361R-SMA mice live 2-3-times longer than P361R-Farber mice and have different phenotypes including progressive ataxia and bladder dysfunction, which suggests neurological dysfunction. We found profound demyelination, loss of axons, and altered sphingolipid levels in P361R-SMA spinal cords; severe pathology was restricted to the white matter. Our model can serve as a tool to study the pathological effects of ACDase deficiency on the central nervous system and to evaluate potential therapies for SMA-PME.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Atrofia Muscular Espinal
/
Epilepsias Mioclónicas Progresivas
/
Lipogranulomatosis de Farber
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Commun Biol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Canadá