Muscle Transcriptomic Study of A Novel Lama2-Related Congenital Muscular Dystrophy Mouse Model

Objectives: To analyze the muscle transcriptome data of a novel mouse model of LAMA2-CMD, dyH/dyH, to explore the pathogenesis of muscle disorders. Methods: The comparison of muscle changes between dyH/dyH and wild-type mice at 2-week-old detected by RNA sequencing, Immunofluorescence and western blot were analyzed. Results: Compared with wild-type mice, the expressions of genes associtated with muscle cytoskeleton and contraction (Myo5c, Myl3, Actc1, Myoz3, Myl2, Myh7, etc.) were downregulated in dyH/dyH mice. Immunofluorescence showed the expressions of MyHC, desmin and β-tubulin were focally increased in the regeneration area, while desmin and β-tubulin were decreased in mature muscle fibers in dyH/dyH mice. Western blot showed that the expression of MyHC and MYH2 protein were increased, the expression of F-actin was decreased in dyH/dyH mice muscle, desmin and β-tubulin showed no obvious change. The expressions of muscle development-related genes (Myog, Myof, Myh3, Myh8, Myo5a, etc.) were upregulated in dyH/dyH mice by RNA sequencing. Immunofluorescence staining showed the expressions of MyoG, MyoD1 and Myf5 were focally increased, while the decreased expressions of MyoG and MyoD1 in dyH/dyH mice were detected by western blot. In addition, the expressions of many genes related to muscle cell membrane ion channels, membrane transporters and mitochondrial energy metabolism were downregulated in dyH/dyH mice. Conclusion: We provided important information about the pathogenesis of LAMA2-CMD based on muscle transcriptomic data of a novel mouse model.