Publication: Dissecting the transcriptional program of phosphomannomutase 2-deficient cells: Lymphoblastoide B cell lines as a valuable model for congenital disorders of glycosylation studies
Authors
Parrado, Antonio ; Serrano, Mercedes ; De la Morena-Barrio, María Eugenia ; Ibáñez-Micó, Salvador ; Ruiz-Lafuente, Natalia ; Schwartz-Albiez, Reinhard ; Esteve-Solé, Ana ; Alsina, Laia ; Corral, Javier ; Hernández Caselles, Trinidad ; Rubio Pedraza, Gonzalo
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Publisher
Oxford University Press
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DOI
https://doi.org/10.1093/glycob/cwab087
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info:eu-repo/semantics/article
Description
©<2022>. This manuscript version is made available under the CC-BY-NC 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This document is the, Accepted, version of a Published Work that appeared in final form in Glycobiology. To access the final edited and published work see: https://doi.org/10.1093/glycob/cwab087
Abstract
Congenital disorders of glycosylation (CDG) include 150 disorders constituting in genetically and
clinically heterogeneous diseases, showing significant glycoprotein hypoglycosylation that leads
to pathological consequences on multiple organs and systems whose underlying mechanisms
are not yet understood. A few cellular and animal models have been used to study specific
CDG characteristics, although they have given limited information due to the few CDG mutations
tested and the still missing comprehensive molecular and cellular basic research. Here, we
provide specific gene expression profiles, based on ribonucleic acid (RNA) microarray analysis,
together with some biochemical and cellular characteristics of a total of nine control Epstein–
Barr virus-transformed lymphoblastoid B cell lines (B-LCL) and 13 CDG B-LCL from patients
carrying severe mutations in the phosphomannomutase 2 (PMM2) gene, strong serum protein
hypoglycosylation and neurological symptoms. Significantly dysregulated genes in PMM2-CDG
cells included those regulating stress responses, transcription factors, glycosylation, motility, cell
junction and, importantly, those related to development and neuronal differentiation and synapse,
such as carbonic anhydrase 2 (CA2) and ADAM23. PMM2-CDG-associated biological consequences
involved the unfolded protein response, RNA metabolism and the endoplasmic reticulum, Golgi
apparatus and mitochondria components. Changes in the transcriptional and CA2 protein levels
are consistent with the CDG physiopathology. These results demonstrate the global transcriptional
impact in phosphomannomutase 2-deficient cells, reveal CA2 as a potential cellular biomarker and
confirm B-LCL as an advantageous model for CDG studies.
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Citation
Glicobiology 2022, Volumen: 32, Número: 2, Páginas: 84-100
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/