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Deletion of Galgt2 (B4Galnt2) reduces muscle growth in response to acute injury and increases muscle inflammation and pathology in dystrophin-deficient mice.
Xu, Rui; Singhal, Neha; Serinagaoglu, Yelda; Chandrasekharan, Kumaran; Joshi, Mandar; Bauer, John A; Janssen, Paulus M L; Martin, Paul T.
Afiliación
  • Xu R; Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
  • Singhal N; Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
  • Serinagaoglu Y; Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
  • Chandrasekharan K; Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
  • Joshi M; Department of Pediatrics, University of Kentucky College of Medicine, Kentucky Children's Hospital, Lexington, Kentucky.
  • Bauer JA; Department of Pediatrics, University of Kentucky College of Medicine, Kentucky Children's Hospital, Lexington, Kentucky.
  • Janssen PM; Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, Ohio.
  • Martin PT; Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio; Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, Ohio; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio. Electr
Am J Pathol ; 185(10): 2668-84, 2015 Oct.
Article en En | MEDLINE | ID: mdl-26435413
ABSTRACT
Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle stimulates the glycosylation of α dystroglycan (αDG) and the up-regulation of laminin α2 and dystrophin surrogates known to inhibit muscle pathology in mouse models of congenital muscular dystrophy 1A and Duchenne muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally increased in the mdx mouse model of Duchenne muscular dystrophy compared with the wild-type mice. To assess whether this increased endogenous Galgt2 expression could affect disease, we quantified muscular dystrophy measures in mdx mice deleted for Galgt2 (Galgt2(-/-)mdx). Galgt2(-/-) mdx mice had increased heart and skeletal muscle pathology and inflammation, and also worsened cardiac function, relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also slowed skeletal muscle growth in response to acute muscle injury. In each instance where Galgt2 expression was elevated (developing muscle, regenerating muscle, and dystrophic muscle), Galgt2-dependent glycosylation of αDG was also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle pathology in dystroglycan-deficient muscles, in contrast to previous studies in dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene expression and glycosylation of αDG are dynamically regulated in muscle and that endogenous Galgt2 gene expression can ameliorate the extent of muscle pathology, inflammation, and dysfunction in mdx mice.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Distrofina / Glicosiltransferasas / Músculo Esquelético / Distrofia Muscular de Duchenne Límite: Animals Idioma: En Revista: Am J Pathol Año: 2015 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Distrofina / Glicosiltransferasas / Músculo Esquelético / Distrofia Muscular de Duchenne Límite: Animals Idioma: En Revista: Am J Pathol Año: 2015 Tipo del documento: Article