Assessment of DNA Variations From Two In Vivo Skeletal Muscle Disorder Mouse Models Using Complementary Square-Wave...

Duchenne Muscular Dystrophy (DMD) and Ehlers-Danlos Syndrome (EDS) are characterized by genetic instability due to DNA damage leading to loss of muscular function. Genetic impacts of these diseases were probed by extracting DNA from selected muscle tissues of either a mouse model of X chromosome-linked muscular dystrophy (mdx, DMD model) or a heterozygous col5a1 (+/-) mouse (EDS model). Complementary square wave voltammetry (SWV) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) approaches were used to assess extracted DNA. SWV analysis was performed by immobilizing DNA layer-by-layer (LbL) on pyrolytic graphite (PG) electrodes before oxidation in the presence of Ru(bpy)₃ ²⁺. Changes in SWV peak currents (I_p) at ∼+1.05 V vs. SCE indicated significant DNA alterations in the genetically altered mouse tissues compared to wild type (WT) controls. Both mdx and heterozygous col5a1(+/-) samples exhibited statistically significant decreased I_p levels (p < 0.05) compared to WT DNA suggesting guanine content varied due to the genetic alterations, which was statistically more significant in leg muscle DNA. MS/MS validated and expanded on the SWV results. DNA base analysis showed increased oxidative damage alongside changes in undamaged base content in mdx mice. DNA from col5a1(+/-) leg muscles exhibited significant changes to undamaged base content, showcasing similar trends.