title: Decreased mAKAP, ryanodine receptor, and SERCA2a gene expression in mdx hearts.
abstract: 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.
mesh_terms: D000818:Animals; D001483:Base Sequence; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D017931:DNA Primers; D015536:Down-Regulation; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009137:Muscular Dystrophy, Animal / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D010656:Phenylephrine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases