Alpha-distroglycanopathies: pathophysiology, genetics and studies in animal models. (Q3202992): Difference between revisions
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(Created claim: summary (P836): Dystroglycanopathies (DGPs) are a heterogeneous group of recessive neuromuscular dystrophys that affect the muscle, brain and retina, and originate from an abnormal alpha-distroglycan O-glycosylation (alpha-DG). This post-translational modification is essential for anchoring muscle and nerve cells to the extracellular matrix, and 18 associated genes have been described as responsible. Since the gene mutated in 60 % of patients with PDD is still...) |
(Changed label, description and/or aliases in en: translated_label) |
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Alpha-distroglycanopathies: pathophysiology, genetics and studies in animal models. | |||
Revision as of 00:54, 13 October 2021
Project Q3202992 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Alpha-distroglycanopathies: pathophysiology, genetics and studies in animal models. |
Project Q3202992 in Spain |
Statements
39,750.0 Euro
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79,500.0 Euro
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50.0 percent
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1 January 2016
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16 December 2018
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UNIVERSIDAD AUTONOMA DE MADRID
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40°25'0.12"N, 3°42'12.89"W
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28079
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Las distroglicanopatías (DGPs) son un grupo heterogéneo de distrofias neuromusculares recesivas que afectan al músculo, cerebro y retina, y están originadas por una O-glicosilación anormal del alfa-distroglicano (alfa-DG). Esta modificación post-traduccional es esencial para el anclaje de las células musculares y nerviosas a la matriz extracelular, y se han descrito como responsables 18 genes asociados. Dado que aún se desconoce el gen mutado en un 60% de los enfermos con DGPs, se llevará a cabo un escrutinio mutacional de enfermos con distintas distrofias de este tipo, orientado también a la búsqueda de nuevos genes causantes de las mismas con fines diagnósticos. Por otra parte, para comprender la fisiopatología de estos procesos se llevarán a cabo estudios en células en cultivo y en animales modelo. Se propone, así, estudiar la función aún desconocida de FKTN (fukutina) y FKRP en la O-glicosilación del alfa-DG, mediante glicómica comparativa y análisis transcriptómico (RNA-Seq) llevados a cabo en mioblastos de ratón C2C12 KO para estos genes. Asimismo, se estudiará la función de POMT1, la primera y más importante enzima en dicho proceso, en modelos animales de ratón KO condicionales en la retina (fotorreceptores y glía de Mu¨ller), músculo esquelético y cardíaco, tejidos en los cuales se caracterizarán las alteraciones moleculares, estructurales y funcionales derivadas de la inactivación de dicho gen. Finalmente, en fotorreceptores en cultivo de la línea 661W, en la cual hemos detectado en el núcleo la presencia de numerosas proteínas asociadas a DGPs, trataremos de identificar nuevos sustratos de estas últimas e investigaremos su posible papel modulador de la proliferación celular y de la expresión génica (Spanish)
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Dystroglycanopathies (DGPs) are a heterogeneous group of recessive neuromuscular dystrophys that affect the muscle, brain and retina, and originate from an abnormal alpha-distroglycan O-glycosylation (alpha-DG). This post-translational modification is essential for anchoring muscle and nerve cells to the extracellular matrix, and 18 associated genes have been described as responsible. Since the gene mutated in 60 % of patients with PDD is still unknown, a mutational screening of patients with different dystrophys of this type will be carried out, also aimed at finding new genes that cause them for diagnostic purposes. On the other hand, to understand the pathophysiology of these processes, studies will be carried out in cells in culture and in model animals. It is proposed, therefore, to study the still unknown function of FKTN (fukutin) and FKRP in the O-glycosylation of alpha-DG, using comparative glycomics and transcriptomic analysis (RNA-Seq) carried out in mouse myoblasts C2C12 KO for these genes. In addition, the role of POMT1, the first and most important enzyme in this process, will be studied, in animal models of conditional mouse KO in the retina (fotorreceptors and glía de Mu▷ller), skeletal and cardiac muscle, tissues in which molecular, structural and functional alterations resulting from the inactivation of this gene will be characterised. Finally, in photoreceptors in cultivation of the 661 W line, in which we have detected in the nucleus the presence of numerous proteins associated with DGPs, we will try to identify new substrates of the latter and investigate their possible modulating role of cell proliferation and gene expression (English)
13 October 2021
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Madrid
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Identifiers
PI15_00073
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