Abstract
BackgroundThe 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.MethodsWe disrupted the Stac3 gene in 4-week-old male mice using the Flp-FRT and tamoxifen-inducible Cre-loxP systems.ResultsRT-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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-016-0088-4) contains supplementary material, which is available to authorized users.
Highlights
The SH3 and cysteine-rich domain 3 (Stac3) gene is expressed in the skeletal muscle
Our study demonstrates that STAC3 is important to fiber hypertrophy, fiber-type composition, muscle contraction, and electrostimulation-induced calcium release from the sarcoplasmic reticulum in the postnatal skeletal muscle
By crossing Stac3+/− mice first with mice expressing the Flp recombinase (TgFlp) and mice expressing the tamoxifen-inducible Cre recombinase (TgCre), we generated mice with the following genotypes: Stac3fl/flTgCre, which were homozygous for the floxed Stac3 allele and carried the Cre recombinase transgene; Stac3+/flTgCre, which were heterozygous for the floxed Stac3 allele and carried the Cre recombinase transgene; and Stac3fl/fl, which were homozygous for the floxed Stac3 allele but did not carry the Cre recombinase transgene
Summary
The SH3 and cysteine-rich domain 3 (Stac3) gene is expressed in the skeletal muscle. We determined the potential role of Stac in postnatal skeletal muscle growth, fiber composition, and contraction by generating conditional Stac knockout mice. The Stac gene, which encodes a protein containing Src homology 3 and cysteine-rich domains, is expressed in the skeletal muscle [1]. STAC3 has been recently identified as a novel regulator of embryonic skeletal muscle development and contraction. Most of the muscle fibers in newborn Stac knockout mice contain centralized nuclei and disorganized myofibrils [1]. The skeletal muscles from Stac3-deleted mouse fetuses do not contract, and this is suggested to be due to defective excitation-contraction (EC) coupling [2].
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