2026-04-14T02:46:43Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4273592026-03-30T04:03:31Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Servián Morilla, Emilia author Takeuchi, Hideyuki author Lee, Tom V. author Clarimón, Jordi author Mavillard, Fabiola author Area Gómez, Estela author Rivas, Eloy author Nieto González, José L. author Rivero, María C. author Cabrera-Serrano, Macarena author Gómez Sánchez, Leonardo author Martínez López, José A. author Estrada, Beatriz author Márquez, Celedonio author Morgado, Yolanda author Suarez-Calvet, Xavier author Pita, Guillermo author Bigot, Anne author Gallardo, Eduard author Fernandez-Chacon, Rafael author Hirano, Michio author Haltiwanger, Robert S. author Jafar-Nejad, Hamed author Paradas, Carmen author Universitat Autònoma de Barcelona author 2016 Skeletal muscle regeneration by muscle satellite cells is a physiological mechanism activated upon muscle damage and regulated by Notch signaling. In a family with autosomal recessive limb-girdle muscular dystrophy, we identified a missense mutation in 1 (protein O -glucosyltransferase 1), an enzyme involved in Notch posttranslational modification and function. In vitro and in vivo experiments demonstrated that the mutation reduces O -glucosyltransferase activity on Notch and impairs muscle development. Muscles from patients revealed decreased Notch signaling, dramatic reduction in satellite cell pool and a muscle-specific α-dystroglycan hypoglycosylation not present in patients' fibroblasts. Primary myoblasts from patients showed slow proliferation, facilitated differentiation, and a decreased pool of quiescent 7 + cells. A robust rescue of the myogenesis was demonstrated by increasing Notch signaling. None of these alterations were found in muscles from secondary dystroglycanopathy patients. These data suggest that a key pathomechanism for this novel form of muscular dystrophy is Notch-dependent loss of satellite cells. Muscular dystrophy Notch O -glycosylation Satellite cell Development & Differentiation Musculoskeletal System A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss