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Role of SH3 and Cysteine-Rich Domain 3 (STAC3) in Skeletal Muscle Development, Postnatal Growth and Contraction

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dc.contributor.authorCong, Xiaofeien
dc.contributor.committeechairJiang, Honglinen
dc.contributor.committeememberGerrard, David E.en
dc.contributor.committeememberChin, Eva R.en
dc.contributor.committeememberGrange, Robert W.en
dc.contributor.committeememberAkers, Robert Michaelen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessioned2017-07-26T06:00:21Zen
dc.date.available2017-07-26T06:00:21Zen
dc.date.issued2016-02-01en
dc.description.abstractThe SH3 and cysteine rich domain 3 (Stac3) gene is expressed specifically in skeletal muscle and essential for skeletal muscle contraction and postnatal life in mice. In this dissertation project, I conducted two studies to further understand the role of STAC3 in skeletal muscle development, growth, and contraction. In the first study, I compared the contractile responses of hindlimb muscles of Stac3 knockout and control mice to electrical stimulation, high [K+]-induced membrane depolarization, and caffeine and 4-chloro-m-cresol (4-CMC) activation of ryanodine receptor (RyR). Frequent electrostimulation-, high [K+]-, 4-CMC- and caffeine-induced maximal tensions in Stac3-deleted muscles were approximately 20%, 29%, 58% and 55% of those in control muscles, respectively. 4-CMC- and caffeine-induced increases in intracellular calcium were not different between Stac3-deleted and control myotubes. Myosin-ATPase and NADH-tetrazolium reductase staining as well as gene expression analyses revealed that Stac3-deleted hindlimb muscles contained more slow type-like fibers than control muscles. These data together confirm a role of STAC3 in EC coupling but also suggest that defective EC coupling is only partially responsible for the significantly reduced contractility in Stac3-deleted hindlimb muscles. In the second study, I determined the potential role of STAC3 in postnatal skeletal muscle growth, fiber composition, and contraction by disrupting Stac3 gene expression in postnatal mice through the Flp-FRT and tamoxifen-inducible Cre-loxP systems. 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 without affecting the total myofiber number. Postnatal Stac3 deletion decreased limb muscle strength. Postnatal Stac3 deletion reduced electrostimulation- but not caffeine-induced maximal force output in limb muscles. Similarly, postnatal Stac3 deletion reduced electrostimulation- but not caffeine-induced calcium release from the sarcoplasmic reticulum. These results demonstrate that STAC3 is important to myofiber hypertrophy, myofiber type composition, contraction, and EC coupling in postnatal skeletal muscle.en
dc.description.degreePh. D.en
dc.format.mediumETDen
dc.identifier.othervt_gsexam:6561en
dc.identifier.urihttp://hdl.handle.net/10919/78432en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectStac3en
dc.subjectmuscle contractionen
dc.subjectEC couplingen
dc.subjectmuscle fiber typeen
dc.subjectmuscle growthen
dc.titleRole of SH3 and Cysteine-Rich Domain 3 (STAC3) in Skeletal Muscle Development, Postnatal Growth and Contractionen
dc.typeDissertationen
thesis.degree.disciplineAnimal and Poultry Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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