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Updated: Aug 29, 2025
Myo-mechanical Analysis of Isolated Skeletal Muscle
Published on: February 22, 2011
Sarco(endo)plasmic reticulum Ca2+-ATPase function is impaired in skeletal and cardiac muscles from young DBA/2J mdx
Riley E G Cleverdon1,2, Jessica L Braun1,2,3, Mia S Geromella1,2
1Department of Kinesiology, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, ON, L2S 3A1, Canada.
Abstract:
The DBA/2J (D2) mdx mouse is 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. Both D2 and C57 mdx mice exhibited signs of impaired Ca2+ uptake in the gastrocnemius, diaphragm, and left ventricle; however, the level of impairment was more severe in D2 mdx mice. Reductions in maximal SERCA activity were also more prominent in the D2 mdx gastrocnemius and diaphragm when compared to those from C57 mdx mice; however, there were no differences detected in the left ventricle. Across all muscles, D2 mdx mice had the highest levels of oxidative stress as indicated by protein nitrosylation and/or nitration. In conclusion, our study shows that SERCA function is more impaired in young D2 mdx mice compared with age-matched C57 mdx mice.
Insights
The DBA/2J (D2) mdx mouse model shows more severe sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) dysfunction and oxidative stress than the C57BL/10 (C57) mdx model. This indicates a more profound impairment in calcium handling in D2 mdx mice.
Area of Science:
- Biochemistry
- Cell Biology
- Animal Models of Disease
Background:
- Duchenne muscular dystrophy (DMD) is a severe genetic disorder.
- The DBA/2J (D2) mdx mouse is a more severe model of DMD than the C57BL/10 (C57) mdx mouse.
- Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) is critical for muscle function by regulating calcium levels.
Purpose of the Study:
- To investigate differences in SERCA function between young D2 mdx and C57 mdx mice.
- To assess the severity of calcium uptake impairment in various muscles of these mouse models.
- To evaluate the extent of oxidative stress in D2 mdx mice compared to C57 mdx mice.
Main Methods:
- Comparative analysis of SERCA activity in gastrocnemius, diaphragm, and left ventricle muscles.
- Measurement of Ca2+ uptake and maximal SERCA activity.
- Assessment of oxidative stress through protein nitrosylation and/or nitration.
Main Results:
- Both D2 and C57 mdx mice displayed impaired Ca2+ uptake, with D2 mdx mice showing more severe impairment.
- Maximal SERCA activity was significantly reduced in the gastrocnemius and diaphragm of D2 mdx mice.
- D2 mdx mice exhibited higher levels of oxidative stress across all tested muscles.
Conclusions:
- SERCA function is more severely impaired in young D2 mdx mice compared to age-matched C57 mdx mice.
- The D2 mdx mouse model presents a more pronounced deficit in calcium handling and increased oxidative stress.
- These findings highlight the utility of the D2 mdx model for studying severe forms of muscular dystrophy.
