title: Sparing of the extraocular muscles in mdx mice with absent or reduced utrophin expression: A life span analysis.
abstract: Sparing of the extraocular muscles in muscular dystrophy is controversial. To address the potential role of utrophin in this sparing, mdx:utrophin(+/-) and mdx:utrophin(-/-) mice were examined for changes in myofiber size, central nucleation, and Pax7-positive and MyoD-positive cell density at intervals over their life span. Known to be spared in the mdx mouse, and contrary to previous reports, the extraocular muscles from both the mdx:utrophin(+/-) and mdx:utrophin(-/-) mice were also morphologically spared. In the mdx:utrophin(+/)(-) mice, which have a normal life span compared to the mdx:utrophin(-/-) mice, the myofibers were larger at 3 and 12 months than the wild type age-matched eye muscles. While there was a significant increase in central nucleation in the extraocular muscles from all mdx:utrophin(+/)(-) mice, the levels were still very low compared to age-matched limb skeletal muscles. Pax7- and MyoD-positive myogenic precursor cell populations were retained and were similar to age-matched wild type controls. These results support the hypothesis that utrophin is not involved in extraocular muscle sparing in these genotypes. In addition, it appears that these muscles retain the myogenic precursors that would allow them to maintain their regenerative capacity and normal morphology over a lifetime even in these more severe models of muscular dystrophy.
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA; Graduate Program in Molecular, Cellular, Developmental Biology and Genetics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Abby A
authors.initials: AA
authors.lastname: McDonald
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Sadie L
authors.initials: SL
authors.lastname: Hebert
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA; Graduate Program in Molecular, Cellular, Developmental Biology and Genetics, University of Minnesota, Minneapolis, MN, USA; Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA. Electronic address: mcloo001@umn.edu.
authors.forename: Linda K
authors.initials: LK
authors.lastname: McLoon
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D003094:Collagen / Q000378:metabolism; D005355:Fibrosis; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D017570:MyoD Protein / Q000378:metabolism; D009801:Oculomotor Muscles / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology*; D009929:Organ Size; D051763:PAX7 Transcription Factor / Q000378:metabolism; D049411:Utrophin / Q000235:genetics / Q000378:metabolism*
chemical_list: D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D049411:Utrophin; D003094:Collagen
keywords: Extraocular muscle; Muscular dystrophy; MyoD; Pax7; Satellite cell; Utrophin