Cell-type-specific dysregulation of RNA alternative splicing in short tandem repeat mouse knockin models of myotonic dystrophy.

Autor:	Nutter CA; Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, Gainesville, Florida 32610, USA., Bubenik JL; Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, Gainesville, Florida 32610, USA., Oliveira R; Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, Gainesville, Florida 32610, USA., Ivankovic F; Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, Gainesville, Florida 32610, USA., Sznajder ŁJ; Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, Gainesville, Florida 32610, USA., Kidd BM; Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, Gainesville, Florida 32610, USA., Pinto BS; Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, Gainesville, Florida 32610, USA., Otero BA; Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, Gainesville, Florida 32610, USA., Carter HA; Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, Gainesville, Florida 32610, USA., Vitriol EA; Department of Anatomy and Cell Biology, University of Florida, Gainesville, Florida 32610, USA., Wang ET; Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, Gainesville, Florida 32610, USA., Swanson MS; Department of Molecular Genetics and Microbiology, Center for NeuroGenetics and the Genetics Institute, University of Florida, Gainesville, Florida 32610, USA.
Jazyk:	angličtina
Zdroj:	Genes & development [Genes Dev] 2019 Dec 01; Vol. 33 (23-24), pp. 1635-1640. Date of Electronic Publication: 2019 Oct 17.
DOI:	10.1101/gad.328963.119
Abstrakt:	Short tandem repeats (STRs) are prone to expansion mutations that cause multiple hereditary neurological and neuromuscular diseases. To study pathomechanisms using mouse models that recapitulate the tissue specificity and developmental timing of an STR expansion gene, we used rolling circle amplification and CRISPR/Cas9-mediated genome editing to generate Dmpk CTG expansion (CTG exp ) knockin models of myotonic dystrophy type 1 (DM1). We demonstrate that skeletal muscle myoblasts and brain choroid plexus epithelial cells are particularly susceptible to Dmpk CTG exp mutations and RNA missplicing. Our results implicate dysregulation of muscle regeneration and cerebrospinal fluid homeostasis as early pathogenic events in DM1. (© 2019 Nutter et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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