title: In vivoimaging of skeletal muscle in mice highlights muscle defects in a model of myotubular myopathy.
abstract: Skeletal muscle structure and function are altered in different myopathies. However, the understanding of the molecular and cellular mechanisms mainly rely onin vitroandex vivoinvestigations in mammalian models. In order to monitorin vivothe intracellular structure of the neuromuscular system in its environment under normal and pathological conditions, we set-up and validated non-invasive imaging of ear and leg muscles in mice. This original approach allows simultaneous imaging of different cellular and intracellular structures such as neuromuscular junctions and sarcomeres, reconstruction of the 3D architecture of the neuromuscular system, and video recording of dynamic events such as spontaneous muscle fiber contraction. Second harmonic generation was combined with vital dyes and fluorescent-coupled molecules. Skin pigmentation, although limiting, did not prevent intravital imaging. Using this versatile toolbox on theMtm1knockout mouse, a model for myotubular myopathy which is a severe congenital myopathy in human, we identified several hallmarks of the disease such as defects in fiber size and neuromuscular junction shape. Intravital imaging of the neuromuscular system paves the way for the follow-up of disease progression or/and disease amelioration upon therapeutic tests. It has also the potential to reduce the number of animals needed to reach scientific conclusions.
authors.affiliation: Inserm U1109, MN3T, Strasbourg, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France; LabEx Medalis, Université de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Mercier
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France; Collège de France, Chaire de Génétique Humaine, Illkirch, France.
authors.forename: Johann
authors.initials: J
authors.lastname: Böhm
authors.affiliation: Inserm U1109, MN3T, Strasbourg, France; LabEx Medalis, Université de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: Nina
authors.initials: N
authors.lastname: Fekonja
authors.affiliation: Inserm U1109, MN3T, Strasbourg, France; LabEx Medalis, Université de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Allio
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Lutz
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Koch
authors.affiliation: Inserm U1109, MN3T, Strasbourg, France; LabEx Medalis, Université de Strasbourg, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France.
authors.forename: Jacky G
authors.initials: JG
authors.lastname: Goetz
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France; Collège de France, Chaire de Génétique Humaine, Illkirch, France.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Laporte
keywords: X-linked myotubular myopathy; centronuclear myopathy; intravital imaging; myotubularin; neuromuscular junction