Myocyte-derived Myomaker expression is required for regenerative fusion but exacerbates membrane instability in dystrophic myofibers

• DOI: 10.1172/jci.insight.136095
• Publication Date: 2020-04-20T20:33:09Z
• Authors: Michael J. Petrany; Taejeong Song; Sakthivel Sadayappan; Douglas P. Millay
• Keywords: Cell fusion; Multinucleate; mdx mouse

Muscle progenitor cell fusion is required for the formation and regeneration of multinucleated skeletal muscle fibers. Chronic in Duchenne muscular dystrophy (DMD) characterized by ongoing satellite (SC) progeny, but effects on disease mechanisms which accomplished this setting are not fully understood. Using mdx mouse model DMD, we deleted fusogenic protein Myomaker SCs or myofibers. Following deletion SCs, mice displayed a complete lack myocyte fusion, resulting severe loss, enhanced fibrosis, significant functional decline. Reduction mature myofibers mice, however, led to minimal alterations dynamics. Unexpectedly, myofiber-specific resulted improvement phenotype, with function decreased damage. Our data indicate that has divergent dystrophic severity depending upon its compartment expression. These findings show absolutely effective persistent expression due may have unintended deleterious consequences integrity. Thus, sustained activation component myogenic program exacerbates disease.