Reduced life span with heart and muscle dysfunction in Drosophila sarcoglycan mutants

Abstract

In humans, genetically diverse forms of muscular dystrophy are associated with a disrupted sarcoglycan complex. The sarcoglycan complex resides at the muscle plasma membrane where it associates with dystrophin. There are six known sarcoglycan proteins in mammals whereas there are only three in Drosophila melanogaster. Using imprecise P element excision, we generated three different alleles at the Drosophila delta-sarcoglycan locus. Each of these deletions encompassed progressively larger regions of the delta-sarcoglycan gene. Line 840 contained a large deletion of the delta-sarcoglycan gene, and this line displayed progressive impairment in locomotive ability, reduced heart tube function and a shortened life span. In line 840, deletion of the Drosophila delta-sarcoglycan gene produced disrupted flight muscles with shortened sarcomeres and disorganized M lines. Unlike mammalian muscle where degeneration is coupled with ongoing regeneration, no evidence for regeneration was seen in this Drosophila sarcoglycan mutant. In contrast, line 28 was characterized with a much smaller deletion that affected only a portion of the cytoplasmic region of the delta-sarcoglycan protein and left intact the transmembrane and extracellular domains. Line 28 had a very mild phenotype with near normal life span, intact cardiac function and normal locomotive activity. Together, these data demonstrate the essential nature of the transmembrane and extracellular domains of Drosophila delta-sarcoglycan for normal muscle structure and function.

Cardiomyopathy Is Associated with Ribosomal Protein Gene Haplo-Insufficiency inDrosophila melanogaster

“…Previous work has found that alterations in structural and contractile proteins can alter contractility in the Drosophila heart (Wolf et al 2006;Allikian et al 2007;Taghli-Lamallem et al 2008). Additionally, signaling in such pathways as Notch, Rhomboid 3, SMAD, and insulin can change heart function in flies (Wessells et al 2004;Kim et al 2010;Yu et al 2010;Goldstein et al 2011).…”

Influence of ovarian muscle contraction and oocyte growth on egg chamber elongation in Drosophila

“…Drosophila has been a useful model for the study of muscular dystrophy, as mutations in homologs of several human disease genes also cause dystrophic phenotypes in flies (Plantié et al, 2015). For example, mutations in dystrophin (Duchenne muscular dystrophy), sarcoglycan gamma and/or delta (limb girdle muscular dystrophy), protein O-mannosyltransferase 1/2 (Walker-Wardburg Syndrome), and lamin A/C (Emery-Dreifuss muscular dystrophy) all show this property (Allikian et al, 2007;Dialynas et al, 2010;Haines et al, 2007;Shcherbata et al, 2007). Wb is the homolog of human laminin subunit alpha 2 (Martin et al, 1999).…”

The Dystrophin Complex: Structure, Function, and Implications for Therapy

“…In zebrafish, five out of the six sarcoglycans have orthologs (38). Three sarcoglycan orthologs have been identified in both Drosophila and C. elegans : one gene similar to mammalian β-sarcoglycan, one gene equally related to mammalian α/ε-sarcoglycan and one to mammalian γ/δ/ζ-sarcoglycan (4, 68). …”