Decreased mAKAP, ryanodine receptor, and SERCA2a gene expression in mdx hearts

Duchenne muscular dystrophy (DMD) is a common genetic disease resulting from mutations in the dystrophin gene. The lack of dystrophin function as a cytoskeletal protein leads to abnormal intracellular Ca 2+ homeostasis, the actual source and functional consequences of which remain obscure. The mdx mouse, a mouse model of DMD, revealed alterations in contractile properties that are likely due to defective Ca 2+ handling. However, the exact mechanisms of the Ca 2+ handling defect are unclear. We performed suppressive subtractive hybridization to isolate differentially expressed genes between 5-month-old mdx and control mice. We observed a decrease in muscle A-kinase anchoring protein (mAKAP) in the mdx hearts. We noticed not only down-regulation of mAKAP mRNA but also decreased mRNA level of the molecules involved in Ca 2+ handling and excitation–contraction (E–C) coupling in the sarcoplasmic reticulum (SR), the cardiac ryanodine receptor, and the sarcoplasmic reticulum Ca 2+ ATPase. Therefore, dystrophin deficiency may cause an impairment of SR Ca 2+ homeostasis and E–C coupling in mdx hearts, in part, by decreased gene expression of molecules involved in SR Ca 2+ handling.