title: Deletion ofPofut1in Mouse Skeletal Myofibers Induces Muscle Aging-Related Phenotypes incisand intrans.
abstract: Sarcopenia, the loss of muscle mass and strength during normal aging, involves coordinate changes in skeletal myofibers and the cells that contact them, including satellite cells and motor neurons. Here we show that the proteinO-fucosyltransferase 1 gene (Pofut1), which encodes a glycosyltransferase required for NotchR-mediated cell-cell signaling, has reduced expression in aging skeletal muscle. Moreover, premature postnatal deletion ofPofut1in skeletal myofibers can induce aging-related phenotypes inciswithin skeletal myofibers and intranswithin satellite cells and within motor neurons via the neuromuscular junction. Changed phenotypes include reduced skeletal muscle size and strength, decreased myofiber size, increased slow fiber (type 1) density, increased muscle degeneration and regeneration in aged muscles, decreased satellite cell self-renewal and regenerative potential, and increased neuromuscular fragmentation and occasional denervation.Pofut1deletion in skeletal myofibers reduced NotchR signaling in young adult muscles, but this effect was lost with age. Increasing muscle NotchR signaling also reduced muscle size. Gene expression studies point to regulation of cell cycle genes, muscle myosins, NotchR and Wnt pathway genes, and connective tissue growth factor byPofut1in skeletal muscle, with additional effects on α dystroglycan glycosylation.
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Zygmunt
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.|Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Singhal
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Mi-Lyang
authors.initials: ML
authors.lastname: Kim
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.|Graduate Program in Molecular Cellular and Developmental Biology, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Cramer
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.|Graduate Program in Molecular Cellular and Developmental Biology, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Crowe
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.|Graduate Program in Molecular Cellular and Developmental Biology, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Adair
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Isabel
authors.initials: I
authors.lastname: Martinez-Pena Y Valenzuela
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.|Hamad Bin Khalifa University, Doha, Qatar.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Akaaboune
authors.affiliation: Center for Human Genetics, Nationwide Children's Hospital, Columbus, Ohio, USA.|Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: White
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Paulus M
authors.initials: PM
authors.lastname: Janssen
authors.affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA Paul.Martin@nationwidechildrens.org.|Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Martin
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005647:Fucosyltransferases / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology*; D009469:Neuromuscular Junction / Q000473:pathology / Q000502:physiology*; D010641:Phenotype; D051880:Receptors, Notch / Q000378:metabolism; D055948:Sarcopenia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D018797:Cell Cycle Proteins; D051880:Receptors, Notch; D005647:Fucosyltransferases; C539426:Pofut1 protein, mouse
keywords: Notch signaling; glycobiology; muscle aging; sarcopenia