Molecular characterization of myotonic dystrophy fibroblast cell lines for use in small molecule screening.
Biochemistry
Molecular physiology
Small molecule
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
20 May 2022
20 May 2022
Historique:
received:
07
04
2021
revised:
30
12
2021
accepted:
01
04
2022
entrez:
28
4
2022
pubmed:
29
4
2022
medline:
29
4
2022
Statut:
epublish
Résumé
Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are common forms of adult onset muscular dystrophy. Pathogenesis in both diseases is largely driven by production of toxic-expanded repeat RNAs that sequester MBNL RNA-binding proteins, causing mis-splicing. Given this shared pathogenesis, we hypothesized that diamidines, small molecules that rescue mis-splicing in DM1 models, could also rescue mis-splicing in DM2 models. While several DM1 cell models exist, few are available for DM2 limiting research and therapeutic development. Here, we characterize DM1 and DM2 patient-derived fibroblasts for use in small molecule screens and therapeutic studies. We identify mis-splicing events unique to DM2 fibroblasts and common events shared with DM1 fibroblasts. We show that diamidines can partially rescue molecular phenotypes in both DM1 and DM2 fibroblasts. This study demonstrates the potential of fibroblasts as models for DM1 and DM2, which will help meet an important need for well-characterized DM2 cell models.
Identifiants
pubmed: 35479399
doi: 10.1016/j.isci.2022.104198
pii: S2589-0042(22)00468-0
pmc: PMC9035709
doi:
Types de publication
Journal Article
Langues
eng
Pagination
104198Subventions
Organisme : NINDS NIH HHS
ID : P50 NS048843
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM121862
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS117910
Pays : United States
Organisme : NINDS NIH HHS
ID : R37 NS040389
Pays : United States
Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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