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Abstract: Sarco(endo)plasmic reticulum calcium ATPases (SERCA) are cellular pumps that transport Ca2+ into the sarcoplasmic reticulum (SR). Serca2 is the most widely expressed gene family member. The very early embryonic lethality of Serca2 null mouse embryos has precluded further evaluation of loss of Serca2 function in the context of organ physiology. We have generated mice carrying a conditional Serca2 flox allele which allows disruption of the Serca2 gene in an organ-specific and/or inducible manner. The model was tested by mating Serca2 flox mice with MLC-2v wt/Cre mice and with αMHC-Cre transgenic mice. In heterozygous Serca2 wt/flox MLC-2v wt/Cre mice, the expression of SERCA2a and SERCA2b proteins were reduced in the heart and slow skeletal muscle, in accordance with the expression pattern of the MLC-2v gene. In Serca2 flox/flox Tg(αMHC-Cre) embryos with early homozygous cardiac Serca2 disruption, normal embryonic development and yolk sac circulation was maintained up to at least embryonic stage E10.5. The Serca2 flox mouse is the first murine conditional gene disruption model for the SERCA family of Ca2+ ATPases, and should be a powerful tool for investigating specific physiological roles of SERCA2 function in a range of tissues and organs in vivo both in adult and embryonic stages. [Copyright &y& Elsevier]

It is often assumed that mechanical factors are important for effects of exercise on muscle, but during voluntary training and most experimental conditions the effects could solely be attributed to differences in electrical activity, and direct evidence for a mechanosensory pathway has been scarce. We here show that, in rat muscles stimulated in vivo under deep anesthesia with identical electrical activity patterns, isometric contractions induced twofold more hypertrophy than contractions with 50-60% of the isometric force. The number of myonuclei and the RNA levels of myogenin and myogenic regulatory factor 4 were increased with high load, suggesting that activation of satellite cells is mechano dependent. On the other hand, training induced a major shift in fiber type distribution from type 2b to 2x that was load independent, indicating that the electrical signaling rather than mechanosignaling controls fiber type. RAC-α serine/threonine-protein kinase (Akt) and ribosomal protein S6 kinase β-1 (S6K1) were not significantly differentially activated by load, suggesting that the differences in mechanical factors were not important for activating the Akt/mammalian target of rapamycin/S6K1 pathway. The transmembrane molecule syndecan-4 implied in overload hypertrophy in cardiac muscle was not load dependent, suggesting that mechanosignaling in skeletal muscle is different., (Copyright © 2016 the American Physiological Society.)