title: The SH3 and cysteine-rich domain 3 (Stac3) gene is important to growth, fiber composition, and calcium release from the sarcoplasmic reticulum in postnatal skeletal muscle.
abstract: BACKGROUND
  The SH3 and cysteine-rich domain 3 (Stac3) gene is specifically expressed in the skeletal muscle. Stac3 knockout mice die perinatally. In this study, we determined the potential role of Stac3 in postnatal skeletal muscle growth, fiber composition, and contraction by generating conditional Stac3 knockout mice.
  
  
  METHODS
  We disrupted the Stac3 gene in 4-week-old male mice using the Flp-FRT and tamoxifen-inducible Cre-loxP systems.
  
  
  RESULTS
  RT-qPCR and western blotting analyses of the limb muscles of target mice indicated that nearly all Stac3 mRNA and more than 70 % of STAC3 protein were deleted 4 weeks after tamoxifen injection. Postnatal Stac3 deletion inhibited body and limb muscle mass gains. Histological staining and gene expression analyses revealed that postnatal Stac3 deletion decreased the size of myofibers and increased the percentage of myofibers containing centralized nuclei, with no effect on the total myofiber number. Grip strength and grip time tests indicated that postnatal Stac3 deletion decreased limb muscle strength in mice. Muscle contractile tests revealed that postnatal Stac3 deletion reduced electrostimulation-induced but not the ryanodine receptor agonist caffeine-induced maximal force output in the limb muscles. Calcium imaging analysis of single flexor digitorum brevis myofibers indicated that postnatal Stac3 deletion reduced electrostimulation- but not caffeine-induced calcium release from the sarcoplasmic reticulum.
  
  
  CONCLUSIONS
  This study demonstrates that STAC3 is important to myofiber hypertrophy, myofiber-type composition, contraction, and excitation-induced calcium release from the sarcoplasmic reticulum in the postnatal skeletal muscle.
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA USA.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Cong
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Doering
authors.affiliation: Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD USA.
authors.forename: Davi A G
authors.initials: DA
authors.lastname: Mazala
authors.affiliation: Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD USA.
authors.forename: Eva R
authors.initials: ER
authors.lastname: Chin
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grange
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA USA.
authors.forename: Honglin
authors.initials: H
authors.lastname: Jiang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000367:Age Factors; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D004558:Electric Stimulation; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006984:Hypertrophy; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction; D024510:Muscle Development / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C529218:CACNA1S protein, mouse; D020746:Calcium Channels, L-Type; D009419:Nerve Tissue Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C583601:STAC3 protein, mouse; C000592747:ryanodine receptor 1, mouse; D002110:Caffeine; D002118:Calcium
keywords: Calcium release; Fiber type; Hypertrophy; Skeletal muscle