title: Impaired muscle regeneration and myoblast differentiation in mice with a muscle-specific KO of IGF-IR.
abstract: IGF-I and its receptor IGF-IR are seen as critical effectors of muscle hypertrophy, a notion recently questioned. Using MKR transgenic mice that express a dominant negative IGF-IR only in skeletal muscle, we have examined the role of the IGF-IR signaling in differentiation and repair of muscle fibers after damage-induced muscle regeneration. This process is impaired in MKR muscle, with incomplete regeneration, persistence of infiltrating cells and sustained expression of differentiation markers. Analysis of MKR and WT muscle-derived progenitor stem cells and myoblasts showed twice as many such cells in MKR muscle and an incomplete in vitro differentiation, that is, despite similar levels of myogenin expression, the level of fusion of MKR myoblasts was significantly reduced in comparison to WT myoblasts. These data show IGF-IR signaling is not only required at early hyperplasia stages of muscle differentiation, but also for late stages of myofiber maturation and hypertrophy.
authors.affiliation: Cell Cycle and Myogenesis, IGH, CNRS UPR 1142, Montpellier, France. Lisa.Heron-Milhavet@igh.cnrs.fr
authors.forename: Lisa
authors.initials: L
authors.lastname: Heron-Milhavet
authors.forename: Daria
authors.initials: D
authors.lastname: Mamaeva
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
authors.forename: Ned J
authors.initials: NJ
authors.lastname: Lamb
authors.forename: Anne
authors.initials: A
authors.lastname: Fernandez
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D055786:Gene Knockout Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000502:physiology
chemical_list: D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1