Article of Significant Interest in This Issue

A New Road to Inducing Therapeutic Surrogate Genes in Skeletal Muscle

Many surrogate genes shown to inhibit muscular dystrophy are normally concentrated at the neuromuscular junction in adult skeletal muscle, which also contains a unique glycan synthesized by GALGT2. GALGT2 overexpression itself induces the overexpression of many such surrogate genes and can inhibit muscular dystrophy. Cramer et al. (e00140-19) identify the first protein, heparin-binding epidermal growth factor-like growth factor (HB-EGF), known to induce endogenous GALGT2 expression in skeletal muscle. They show that HB-EGF increases GALGT2 expression via an EGF receptor-Akt-TFAP4 signaling pathway and that HB-EGF deletion mimics deletion of GALGT2 with respect to changed glycosylation and changed neuromuscular and muscle phenotypes, including those relevant to muscular dystrophy.