Spinal muscular atrophy-like phenotype in a mouse model of acid ceramidase deficiency. Commun Biol 2023 May 25;6(1):560
Date
05/26/2023Pubmed ID
37231125Pubmed Central ID
PMC10212955DOI
10.1038/s42003-023-04932-wScopus ID
2-s2.0-85160222255 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
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.
Author List
Nagree MS, Rybova J, Kleynerman A, Ahrenhoerster CJ, Saville JT, Xu T, Bachochin M, McKillop WM, Lawlor MW, Pshezhetsky AV, Isaeva O, Budde MD, Fuller M, Medin JAAuthors
Matthew Budde PhD Associate Professor in the Neurosurgery department at Medical College of WisconsinOlena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin
Jitka Rybova Research Scientist I in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsFarber Lipogranulomatosis
Humans
Mice
Muscular Atrophy, Spinal
Myoclonic Epilepsies, Progressive
Phenotype
Sphingolipids
