Figure 1. Mini-Gamma rescues Drosophila muscular dystrophy.

(A) γ-Sarcoglycan (GSG) is a type II transmembrane protein with a cytoplasmic amino-terminus and an extracellular carboxy-terminus. The SGCG gene encoding γ-sarcoglycan is composed of 8 exons, and the most common mutation falls within exon 6 and disrupts the reading frame (15). To restore the reading frame, skipping exon 4–7 is required. This approach removes a portion of the extracellular domain, producing an internally truncated protein, referred to as Mini-Gamma. (B) The GAL4/UAS system was used to express full-length mGSG and Mini-Gamma as transgenes in Sgcd⁸⁴⁰ flies, a sarcoglycan-deficient model of muscular dystrophy. Mini-Gamma protein localized to the plasma membrane in Sgcd⁸⁴⁰ fly skeletal muscle (Mef2-Gal4, UAS-Mini-Gamma), similar to full-length mGSG (Mhc-Gal4, UAS-mGSG). In fly heart tube, Mini-Gamma also showed a plasma membrane staining (TinΔC-Gal4, UAS-Mini-Gamma). Scale bars: 20 μm. (C) OCT was used to measure fly heart function (24). Sgcd⁸⁴⁰ flies had dilated heart tubes with increased ESD compared with WT flies. Expression of Mini-Gamma in the Sgcd⁸⁴⁰ heart tube restored ESD to WT level (Mef-Gal4, UAS-Mini-Gamma) (n = 10~12 flies per genotype). (D) The MB5 monitor was used to record fly spontaneous activity. Nocturnal activity is shown (12 am–8 am). Expression of Mini-Gamma improved nocturnal activity of Sgcd⁸⁴⁰. The degree of rescue was similar between full-length mGSG and Mini-Gamma (n = 20~35 flies per genotype). Student’s t test was used to compare results between 2 groups.