Developmental delay and late onset HBSL pathology in hypomorphic Dars1^M256L mice.

ABSTRACT: The leukodystrophy Hypomyelination with Brainstem and Spinal cord involvement and Leg spasticity (HBSL) is caused by recessive mutations of the DARS1 gene, which encodes the cytoplasmic aspartyl-tRNA synthetase. HBSL is a spectrum disorder with disease onset usually during early childhood and no available treatment options. Patients display regression of previously acquired motor milestones, spasticity, ataxia, seizures, nystagmus, and intellectual disabilities. Gene-function studies in mice revealed that homozygous Dars1 deletion is embryonically lethal, suggesting that successful modelling of HBSL requires the generation of disease-causing genocopies in mice. In this study, we introduced the pathogenic DARS1 ^M256L mutation located on exon nine of the murine Dars1 locus. Despit

SUBMITTER: Klugmann M 

PROVIDER: S-EPMC9217827 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature