Ineffective behavioral rescue despite partial brain Dp427 restoration by AAV9-U7-mediated exon 51 skipping in <i>mdx52</i> mice.

ABSTRACT: The mdx52 mouse model exhibits a common mutation profile associated with brain involvement in Duchenne muscular dystrophy (DMD), characterized by heightened anxiety, fearfulness, and impaired associative fear learning. Deletion of exon 52 disrupts the expression of two dystrophins found in the brain (Dp427 and Dp140) and is eligible for therapeutic exon-skipping strategies. We previously demonstrated that a single intracerebroventricular administration of an antisense oligonucleotide (ASO) targeting exon 51 of the Dmd gene could restore 5%-15% of Dp427 expression. This treatment reduced anxiety and unconditioned fear in mdx52 mice, improved fear conditioning acquisition, and partially improved fear memory tested 24 h later. To improve the restoration of Dp427 and induc

SUBMITTER: Vacca O 

PROVIDER: S-EPMC12718193 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature