ABSTRACT
Postnatal development of skeletal muscle is a highly dynamic period of tissue remodeling. Here, we used RNA-seq to identify transcriptome changes from late embryonic to adult mouse muscle and demonstrate that alternative splicing developmental transitions impact muscle physiology. The first 2 weeks after birth are particularly dynamic for differential gene expression and alternative splicing transitions, and calcium-handling functions are significantly enriched among genes that undergo alternative splicing. We focused on the postnatal splicing transitions of the three calcineurin A genes, calcium-dependent phosphatases that regulate multiple aspects of muscle biology. Redirected splicing of calcineurin A to the fetal isoforms in adult muscle and in differentiated C2C12 slows the timing of muscle relaxation, promotes nuclear localization of calcineurin target Nfatc3, and/or affects expression of Nfatc transcription targets. The results demonstrate a previously unknown specificity of calcineurin isoforms as well as the broader impact of alternative splicing during muscle postnatal development.
Subject(s)
Alternative Splicing , Calcineurin/biosynthesis , Calcium/metabolism , Muscle, Skeletal/growth & development , NFATC Transcription Factors/metabolism , Animals , Animals, Newborn , Calcineurin/genetics , Gene Expression Profiling , MiceABSTRACT
Sarcoidosis is a chronic multisystem granulomatous inflammatory disorder. It can present acutely which is known as Löfgren's syndrome. The diagnosis may be missed if clinicians are not aware of its classic presenting features and the appropriate diagnostic investigations.
Subject(s)
Lymphatic Diseases/diagnostic imaging , Mediastinum/diagnostic imaging , Sarcoidosis/diagnosis , Acute Disease , Adrenal Cortex Hormones/therapeutic use , Analgesics/therapeutic use , Arthritis/drug therapy , Arthritis/etiology , Erythema Nodosum/drug therapy , Erythema Nodosum/etiology , Humans , Lymphatic Diseases/etiology , Respiratory Function Tests , Sarcoidosis/complications , Sarcoidosis/drug therapy , Sarcoidosis, Pulmonary/diagnosis , Sarcoidosis, Pulmonary/drug therapy , Tomography, X-Ray ComputedABSTRACT
Cramps and myalgias have many etiologies. Three cases of hypothyroidism presenting with musculoskeletal symptoms are described. Each case was different in presentation, but all had no weakness but high creatine kinase levels. Treatment with thyroxine resolved all symptoms. These patients emphasize the importance of considering hypothyroidism in anyone with unexplained muscle symptoms.
