title: Muscle-specific deletion of exons 2 and 3 of the IL15RA gene in mice: effects on contractile properties of fast and slow muscles.
abstract: Interleukin-15 (IL-15) is a putative myokine hypothesized to induce an oxidative skeletal muscle phenotype. The specific IL-15 receptor alpha subunit (IL-15Rα) has also been implicated in specifying this contractile phenotype. The purposes of this study were to determine the muscle-specific effects of IL-15Rα functional deficiency on skeletal muscle isometric contractile properties, fatigue characteristics, spontaneous cage activity, and circulating IL-15 levels in male and female mice. Muscle creatine kinase (MCK)-driven IL-15Rα knockout mice (mIl15ra(fl/fl)/Cre(+)) were generated using the Cre-loxP system. We tested the hypothesis that IL-15Rα functional deficiency in skeletal muscle would increase resistance to contraction-induced fatigue, cage activity, and circulating IL-15 levels. There was a significant effect of genotype on the fatigue curves obtained in extensor digitorum longus (EDL) muscles from female mIl15ra(fl/fl)/Cre(+) mice, such that force output was greater during the repeated contraction protocol compared with mIl15ra(fl/fl)/Cre(-) control mice. Muscles from female mIl15ra(fl/fl)/Cre(+) mice also had a twofold greater amount of the mitochondrial genome-specific COXII gene compared with muscles from mIl15ra(fl/fl)/Cre(-) control mice, indicating a greater mitochondrial density in these skeletal muscles. There was a significant effect of genotype on the twitch:tetanus ratio in EDL and soleus muscles from mIl15ra(fl/fl)/Cre(+) mice, such that the ratio was lower in these muscles compared with mIl15ra(fl/fl)/Cre(-) control mice, indicating a pro-oxidative shift in muscle phenotype. However, spontaneous cage activity was not different and IL-15 protein levels were lower in male and female mIl15ra(fl/fl)/Cre(+) mice compared with control. Collectively, these data support a direct effect of muscle IL-15Rα deficiency in altering contractile properties and fatigue characteristics in skeletal muscles.
authors.affiliation: Division of Exercise Physiology, West Virginia University, Morgantown, West Virginia;
authors.forename: Grant
authors.initials: G
authors.lastname: O'Connell
authors.affiliation: Division of Exercise Physiology, West Virginia University, Morgantown, West Virginia;
authors.forename: Ge
authors.initials: G
authors.lastname: Guo
authors.affiliation: Division of Exercise Physiology, West Virginia University, Morgantown, West Virginia; Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia;
authors.forename: Janelle
authors.initials: J
authors.lastname: Stricker
authors.affiliation: Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington; and.
authors.forename: LeBris S
authors.initials: LS
authors.lastname: Quinn
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California.
authors.forename: Averil
authors.initials: A
authors.lastname: Ma
authors.affiliation: Division of Exercise Physiology, West Virginia University, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, West Virginia University, Morgantown, West Virginia; West Virginia Clinical and Translational Science Institute, West Virginia University, Morgantown, West Virginia; epistilli2@hsc.wvu.edu.
authors.forename: Emidio E
authors.initials: EE
authors.lastname: Pistilli
mesh_terms: D000818:Animals; D005091:Exons / Q000235:genetics*; D005260:Female; D019409:Interleukin-15 / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic / Q000235:genetics / Q000502:physiology; D008928:Mitochondria / Q000235:genetics / Q000502:physiology; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology*; D018763:Muscle Fatigue / Q000235:genetics / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology*; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology*; D053647:Receptors, Interleukin-15 / Q000235:genetics
chemical_list: C508025:Il15ra protein, mouse; D019409:Interleukin-15; D053647:Receptors, Interleukin-15
keywords: fatigue; interleukin; isometric contractile properties; myokine