Project description:By comparing the transcriptome from proximal (quadriceps femoris, QF) and distal (tibialis anterior, TA)muscle groups in dysferlin deficient mouse muscle (the SJL mutation bred onto C57BL/10 to produces C57BL/10.SJL_Dysf) with proximal and distal muscle groups from control C57BL/10 mice of an equivalent age (3-weeks old, prior to the onset of overt pathology) we aim to address the issues of muscle selectivity in this this form of muscular dystrophy.
Project description:By comparing the transcriptome from proximal (quadriceps femoris, QF) and distal (tibialis anterior, TA)muscle groups in dysferlin deficient mouse muscle (the SJL mutation bred onto C57BL/10 to produces C57BL/10-SJL.Dysf) with proximal and distal muscle groups from control C57BL/10 mice of an equivalent age (3-weeks old, prior to the onset of overt pathology) we aim to address the issues of muscle selectivity in this this form of muscular dystrophy. Keywords: parallel sample
Project description:Dysferlin is expressed in skeletal and cardiac muscle. However, dysferlin deficiency, namely limb girdle muscular dystrophy 2B (LGMD2B) and Myoshi myopathy, results in skeletal muscle weakness and spares the heart. This dichotomy could be caused by differential regulation of protective mechanisms. Therefore, we compared intraindividual mRNA expression profiles between cardiac and skeletal muscle in dysferlin-deficient SJL/J mice and normal C57BL/6 mice. Keywords: parallel sample
Project description:Dysferlin is expressed in skeletal and cardiac muscle. However, dysferlin deficiency, namely limb girdle muscular dystrophy 2B (LGMD2B) and Myoshi myopathy, results in skeletal muscle weakness and spares the heart. This dichotomy could be caused by differential regulation of protective mechanisms. Therefore, we compared intraindividual mRNA expression profiles between cardiac and skeletal muscle in dysferlin-deficient SJL/J mice and normal C57BL/6 mice. Experiment Overall Design: 20 chips were analyzed. They represent 4 groups of 5 replicates each. Experiment Overall Design: The 4 groups are cardiac (LV) and skeletal muscle of normal and dysferlin deficient mice. Experiment Overall Design: Tissues from normal mice are the controls in comparison to tissues of dysferlin deficient mice.
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from Mus musculus tissues (Heart, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from seven Mus musculus tissues (Heart, Brain, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
Project description:Genome wide expression study of the effect of single stranded RNA (ssRNA) in A/JOlaHsd (WT), A/J and A/J-MyD88 deficient mice. The hypothesis for this study was that endogenous TLR ligands released from the leaking dysferlin-deficient muscle fibers engage TLRs on muscle and immune cells and contribute to disease progression.These data point to a clear role for the TLR pathway in the pathogenesis of dysferlin deficiency.
Project description:LGMD R2 is a rare genetic disorder characterized by progressive proximal muscle weakness and wasting caused by a recessive loss of function of dysferlin, a transmembrane protein controlling plasma membrane repair in skeletal muscles. Despite major advances in biotherapies in recent years, there is currently no curative treatment available for LGMD R2, or dysferlinopathies in general. This failure can be explained in part by our lack of understanding of the functions performed by dysferlin within the muscle fiber. Indeed, despite the identification of dysferlin's role in membrane repair, intracellular vesicular trafficking or calcium homeostasis, we do not know which of these functions or combination of functions is most involved in the pathophysiological development of dysferlinopathies. It also seems highly likely that other dysferlin functions have yet to be discovered. In this aim, we generated hiPSC-derived skeletal muscle model and investigated the molecular consequences associated with loss of dysferlin expression by performing a comparative gene expression profiling between control and LGMD R2 myotubes.
