Journal Article

Reduced life span with heart and muscle dysfunction in <i>Drosophila</i> sarcoglycan mutants

Michael J. Allikian, Gira Bhabha, Patrick Dospoy, Ahlke Heydemann, Pearl Ryder, Judy U. Earley, Matthew J. Wolf, Howard A. Rockman and Elizabeth M. McNally

in Human Molecular Genetics

Volume 16, issue 23, pages 2933-2943
Published in print December 2007 | ISSN: 0964-6906
Published online September 2007 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddm254
Reduced life span with heart and muscle dysfunction in Drosophila sarcoglycan mutants

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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 δ-sarcoglycan locus. Each of these deletions encompassed progressively larger regions of the δ-sarcoglycan gene. Line 840 contained a large deletion of the δ-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 δ-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 δ-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 δ-sarcoglycan for normal muscle structure and function.

Journal Article.  6539 words.  Illustrated.

Subjects: Genetics and Genomics

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