Androgen toxicity on neuromuscular physiology in a novel model of SBMA
U Spinal bulbar and muscular atrophy (SBMA) is a male-specific, late onset disease. It is commonly presumed to be a neurodegenerative disease caused by expression of mutated androgen receptors in motoneurons which leads to their gradual loss. The disease has been characterized by several laboratories using mouse models that universally express androgen receptors with the disease-causing CAG/polyglutamine repeat expansion in the first exon of androgen receptors. Our laboratory has engineered a transgenic mouse model that shows comparable androgen-dependent disease symptoms. However, our model differs from other SBMA mouse models in that our mice over-express the wild type androgen receptor only in skeletal muscle fibers. That our mice show a SBMA disease phenotype suggests that androgen receptors may act in muscle fibers to trigger SBMA. In short, SBMA may have a myogenic origin.