title: A comparative study of N-glycolylneuraminic acid (Neu5Gc) and cytotoxic T cell (CT) carbohydrate expression in normal and dystrophin-deficient dog and human skeletal muscle.
abstract: The expression of N-glycolylneuraminic acid (Neu5Gc) and the cytotoxic T cell (CT) carbohydrate can impact the severity of muscular dystrophy arising from the loss of dystrophin in mdx mice. Here, we describe the expression of these two glycans in skeletal muscles of dogs and humans with or without dystrophin-deficiency. Neu5Gc expression was highly reduced (>95%) in muscle from normal golden retriever crosses (GR, n = 3) and from golden retriever with muscular dystrophy (GRMD, n = 5) dogs at multiple ages (3, 6 and 13 months) when compared to mouse muscle, however, overall sialic acid expression in GR and GRMD muscles remained high at all ages. Neu5Gc was expressed on only a minority of GRMD satellite cells, CD8⁺ T lymphocytes and macrophages. Human muscle from normal (no evident disease, n = 3), Becker (BMD, n = 3) and Duchenne (DMD, n = 3) muscular dystrophy individuals had absent to very low Neu5Gc staining, but some punctate intracellular muscle staining was present in BMD and DMD muscles. The CT carbohydrate was localized to the neuromuscular junction in GR muscle, while GRMD muscles had increased expression on a subset of myofibers and macrophages. In humans, the CT carbohydrate was ectopically expressed on the sarcolemmal membrane of some BMD muscles, but not normal human or DMD muscles. These data are consistent with the notion that altered Neu5Gc and CT carbohydrate expression may modify disease severity resulting from dystrophin deficiency in dogs and humans.
authors: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America ; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, United States of America ; Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.
authors: Paul T
authors: PT
authors: Martin
authors: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors: Bethannie
authors: B
authors: Golden
authors: Departments of Medicine and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, United States of America.
authors: Jonathan
authors: J
authors: Okerblom
authors: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors: Marybeth
authors: M
authors: Camboni
authors: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors: Kumaran
authors: K
authors: Chandrasekharan
authors: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors: Rui
authors: R
authors: Xu
authors: Departments of Medicine and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, United States of America.
authors: Ajit
authors: A
authors: Varki
authors: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America ; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.
authors: Kevin M
authors: KM
authors: Flanigan
authors: Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas, United States of America.
authors: Joe N
authors: JN
authors: Kornegay
mesh_terms: D000818:Animals; D004285:Dogs; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009438:Neuraminic Acids / Q000032:analysis* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000473:pathology*
chemical_list: D016189:Dystrophin; D009438:Neuraminic Acids; C032592:N-glycolylneuraminic acid