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bioRxiv · 10.1101/2021.10.25.465805

SERCA-mediated calcium uptake in the DBA/2J vs C57BL/10 mdx models of Duchenne muscular dystrophy

Cleverdon, R. E.·Whitley, K. C.·Marko, D. M.·Hamstra, S. I.·Braun, J. L.·Roy, B. D.·MacPherson, R. E.·Fajardo, V.
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Abstract

The DBA/2J (D2) mdx mouse has emerged as a more severe model of Duchenne muscular dystrophy when compared to the traditional C57BL/10 (C57) mdx mouse. Here, we questioned whether sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) function would differ in muscles from young D2 and C57 mdx mice. In gastrocnemius muscles, both D2- and C57 mdx mice exhibited signs of impaired Ca2+ uptake, however, this was more severe in D2 mdx mice. Maximal SERCA activity was lowered only in D2 mdx gastrocnemius muscles and not C57 mdx muscles. Furthermore, in the left ventricle and diaphragm, Ca2+ uptake was impaired in C57 mdx muscles with lowered rates of Ca2+ uptake compared with C57 WT mice, whereas in muscles from D2 mdx mice, rates of Ca2+ uptake were unattainable due to the severe impairments in their ability to transport Ca2+. Overall, our study demonstrates that SERCA function is drastically impaired in young D2 mdx mice.

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Cleverdon, R. E., Whitley, K. C., Marko, D. M., Hamstra, S. I., Braun, J. L., Roy, B. D., MacPherson, R. E., Fajardo, V.. 2021-10-26. SERCA-mediated calcium uptake in the DBA/2J vs C57BL/10 mdx models of Duchenne muscular dystrophy. https://doi.org/10.1101/2021.10.25.465805

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