P.90 - Nuclear magnetic resonance relaxometry characterization of D2-mdx mice

Abstract

The C57BL/10-mdx mouse (mdx) is the most frequently studied animal model of Duchenne muscle dystrophy (DMD), where the absence of dystrophin in skeletal muscle leads to inflammation and necrosis in the histological analysis. Nevertheless, mdx mice have an overall benign phenotype, with high rates of muscle regeneration and moderate fibrosis. When in the DBA/2J genetic background (D2-mdx), dystrophin absence leads to a more severe phenotype, in special with increased interstitial fibrosis. The purpose of this study was to characterize D2-mdx mice by nuclear magnetic resonance (NMR) imaging, in comparison to mdx and DBA/2J wild-type mice (WT). Seven D2-mdx, 5 mdx and 5 WT male mice were evaluated at 10 weeks of age. NMR was done under isoflurane anesthesia in a 7T system and included T1 weighted images, T1 and T2 measurements. Four muscle groups were evaluated: tibialis anterior (TA), gastrocnemii (G), quadriceps (Q) and hamstrings (HM). Statistical analysis was performed on SPSS, with 1-factor ANOVA followed by post-hoc Bonferroni multiple comparison test and a correlation analysis between T1 and T2. While D2-mdx mice had similar T1 values as WT mice for all muscles, mdx mice displayed increased T1 when compared to WT mice for TA (p < 0.01), and increased T1 when compared to D2-mdx mice for TA (p < 0.05) and HM (p < 0.01). D2-mdx mice showed higher muscle water T2 in G and HM than WT mice (p < 0.01), and lower water T2 values than mdx in TA, Q and HM muscles (p < 0.01). Water T2 was increased in mdx mice in all muscles when compared to WT mice (p < 0.001). T1 and T2 values correlated for all mouse strains (p < 0.01). Despite the worse phenotype and similar degrees of inflammation and muscle degeneration, D2-mdx mice did not present as high T1 and T2 NMR values as mdx mice. These results indicate that increases in T1 and T2 due to dystrophin absence are partly compensated by additional variables in D2-mdx mice, such as muscle fibrosis.