title: A novel hindlimb immobilization procedure for studying skeletal muscle atrophy and recovery in mouse.
abstract: Skeletal muscle atrophy is a serious concern for patients afflicted by limb restriction due to surgery (e.g., arthrodesis), several articular pathologies (e.g., arthralgia), or simply following cast immobilization. To study the molecular events involved in this immobilization-induced debilitating condition, a convenient mouse model for atrophy is lacking. Here we provide a new immobilization procedure exploiting the normal flexion of the mouse hindlimb using a surgical staple to fix the ventral part of the foot to the distal part of the calf. Histological analysis revealed that our approach induced significant skeletal muscle atrophy by reducing the myofiber size of the tibialis anterior (TA) muscle by 36% compared with the untreated contralateral TA within a few days postimmobilization. Two molecular markers for atrophy, atrogin-1/muscle atrophy F-box (atrogin-1/MAFbx) and muscle ring finger 1 (MuRF-1) mRNAs, were significantly upregulated by 1.9- and 5.9-fold, respectively. Interestingly, our model also revealed the presence of an early inflammatory process during atrophy, characterized by the mRNA upregulation of TNF-alpha, IL-1, and IL-6 (1.9-, 2.4-, and 3.4-fold, respectively) simultaneously with the upregulation of the common leukocyte marker CD45 (6.1-fold). Moreover, muscle rapidly recovered on remobilization, an event associated with significantly increased levels of uncoupling protein-3 and peroxisome proliferator-activated receptor gamma coactivator-1alpha mRNA, key components of prooxidative muscle metabolism. This model offers unexpected new insights into the molecular events involved in immobilization atrophy.
authors.affiliation: Department of Orthopaedic Surgery, Universite de Sherbrooke, Quebec, Canada.
authors.forename: Annabelle Z
authors.initials: AZ
authors.lastname: Caron
authors.forename: Geneviève
authors.initials: G
authors.lastname: Drouin
authors.forename: Justine
authors.initials: J
authors.lastname: Desrosiers
authors.forename: Frédéric
authors.initials: F
authors.lastname: Trensz
authors.forename: Guillaume
authors.initials: G
authors.lastname: Grenier