| First Author | Sznajder ??J | Year | 2025 |
| Journal | Nat Neurosci | Volume | 28 |
| Issue | 6 | Pages | 1199-1212 |
| PubMed ID | 40259070 | Mgi Jnum | J:391981 |
| Mgi Id | MGI:8407346 | Doi | 10.1038/s41593-025-01943-0 |
| Citation | Sznajder LJ, et al. (2025) Autism-related traits in myotonic dystrophy type 1 model mice are due to MBNL sequestration and RNA mis-splicing of autism-risk genes. Nat Neurosci 28(6):1199-1212 |
| abstractText | Genome-wide enrichment of gene-specific tandem repeat expansions has been linked to autism spectrum disorder. One such mutation is the CTG tandem repeat expansion in the 3' untranslated region of the DMPK gene, which is known to cause myotonic muscular dystrophy type 1. Although there is a clear clinical association between autism and myotonic dystrophy, the molecular basis for this connection remains unknown. Here, we report that sequestration of MBNL splicing factors by mutant DMPK RNAs with expanded CUG repeats alters the RNA splicing patterns of autism-risk genes during brain development, particularly a class of autism-relevant microexons. We demonstrate that both DMPK-CTG expansion and Mbnl null mouse models recapitulate autism-relevant mis-splicing profiles, along with social behavioral deficits and altered responses to novelty. These findings support our model that myotonic dystrophy-associated autism arises from developmental mis-splicing of autism-risk genes. |
