| First Author | Nagree MS | Year | 2023 |
| Journal | Commun Biol | Volume | 6 |
| Issue | 1 | Pages | 560 |
| PubMed ID | 37231125 | Mgi Jnum | J:360938 |
| Mgi Id | MGI:7484849 | Doi | 10.1038/s42003-023-04932-w |
| Citation | Nagree MS, et al. (2023) Spinal muscular atrophy-like phenotype in a mouse model of acid ceramidase deficiency. Commun Biol 6(1):560 |
| abstractText | 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. |
