 visitant ::
identificació
|
|||||||||||||||
|
Cerca | Lliura | Ajuda | Servei de Biblioteques | Sobre el DDD | Català English Español | |||||||||
| Pàgina inicial > Articles > Articles publicats > Three-dimensional imaging in myotonic dystrophy type 1 |
(Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa) (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12)) (Institut Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol)| Data: | 2020 |
| Resum: | We aimed to determine whether 3D imaging reconstruction allows identifying molecular:clinical associations in myotonic dystrophy type 1 (DM1). We obtained myoblasts from 6 patients with DM1 and 6 controls. We measured cytosine-thymine-guanine (CTG) expansion and detected RNA foci and muscleblind like 1 (MBNL1) through 3D reconstruction. We studied dystrophia myotonica protein kinase (DMPK) expression and splicing alterations of MBNL1, insulin receptor, and sarcoplasmic reticulum Ca(2+)-ATPase 1. Three-dimensional analysis showed that RNA foci (nuclear and/or cytoplasmic) were present in 45%-100% of DM1-derived myoblasts we studied (range: 0-6 foci per cell). RNA foci represented <0. 6% of the total myoblast nuclear volume. CTG expansion size was associated with the number of RNA foci per myoblast (r = 0. 876 [95% confidence interval 0. 222-0. 986]) as well as with the number of cytoplasmic RNA foci (r = 0. 943 [0. 559-0. 994]). Although MBNL1 colocalized with RNA foci in all DM1 myoblast cell lines, colocalization only accounted for 1% of total MBNL1 expression, with the absence of DM1 alternative splicing patterns. The number of RNA foci was associated with DMPK expression (r = 0. 967 [0. 079-0. 999]). On the other hand, the number of cytoplasmic RNA foci was correlated with the age at disease onset (r = −0. 818 [−0. 979 to 0. 019]). CTG expansion size modulates RNA foci number in myoblasts derived from patients with DM1. MBNL1 sequestration plays only a minor role in the pathobiology of the disease in these cells. Higher number of cytoplasmic RNA foci is related to an early onset of the disease, a finding that should be corroborated in future studies. |
| Ajuts: | Instituto de Salud Carlos III PI15-01756 Instituto de Salud Carlos III PI15-00558 Instituto de Salud Carlos III PI18-00713 Instituto de Salud Carlos III CD14-00032 Instituto de Salud Carlos III CPII19-00021 Instituto de Salud Carlos III CM16-00016 Agència de Gestió d'Ajuts Universitaris i de Recerca FI_B 01090 Agència de Gestió d'Ajuts Universitaris i de Recerca SGR1520(GRC) European Commission 793830 |
| Nota: | Altres ajuts: The research of G. Nogales-Gadea, A. Ramos-Fransi, and A. Lucia is funded by Instituto de Salud Carlos III and cofinanced by Fondos FEDER. G. Nogales-Gadea is supported by a Miguel Servet research contract and by a Trampoline Grant #21108 from AFM Telethon. A. Ballester-Lopez is funded by an FI Agaur fellowship and Generalitat de Catalunya. E. Koehorst is funded by the La Caixa Foundation (ID 100010434), fellowship code LCF/BQ/IN18/11660019, cofunded by the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 713673. I. Linares-Pardo is funded by CP14/00032 and SGR 1520 (GRC) Generalitat de Catalunya. J. Núñez-Manchón was funded by AFM Telethon Trampoline Grant #21108. G. Lucente was supported by a Rio Hortega contract. J. Chojnacki is supported by European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant . The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data. |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Publicat a: | Neurology: Genetics, Vol. 6 (july 2020) , ISSN 2376-7839 |
