Key result
Young D2 mdx mice show drastically impaired muscle SERCA function compared to C57 mdx mice.
Why the study?
The DBA/2J mdx mouse is a more severe model of Duchenne muscular dystrophy than C57BL/10 mdx mice, but whether SERCA function differs between young models was unclear.
Young D2 mdx mice exhibit severe impairments in SERCA function in skeletal and cardiac muscle, providing a possible mechanistic explanation for the worsened pathology and early-onset weakness seen in this severe DMD model.
Impaired SERCA may underlie severe DMD phenotype in D2 mdx mice; hypothesis-generating for therapies but leaves open human translation.
Summary 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 Ca 2+ -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 Ca 2+ 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, Ca 2+ uptake was impaired in C57 mdx muscles with lowered rates of Ca 2+ uptake compared with C57 WT mice, whereas in muscles from D2 mdx mice, rates of Ca 2+ uptake were unattainable due to the severe impairments in their ability to transport Ca 2+ . Overall, our study demonstrates that SERCA function is drastically impaired in young D2 mdx mice.
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Cleverdon et al. (2021) studied Duchenne muscular dystrophy (murine model). DBA/2J (D2) background in mdx mice vs. C57BL/10 (C57) mdx mice and wild-type controls was evaluated on SERCA function and Ca2+ uptake in skeletal and cardiac muscles. SERCA function and Ca2+ uptake were drastically impaired in skeletal and cardiac muscles from young D2 mdx mice compared to C57 mdx mice, potentially contributing to their more severe disease phenotype.
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