Review highlights role of zebrafish and Drosophila studies in understanding muscular dystrophies

Plantié E, Migocka-Patrzałek M, Daczewska M, Jagla K. Model organisms in the fight against muscular dystrophy: lessons from drosophila and Zebrafish. Molecules. 2015 Apr 9;20(4):6237-53. PMID: 25859781.

From the abstract: "Muscular dystrophies (MD) are a heterogeneous group of genetic disorders that cause muscle weakness, abnormal contractions and muscle wasting, often leading to premature death. More than 30 types of MD have been described so far; those most thoroughly studied are Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1) and congenital MDs. ... To improve our knowledge of how MD-caused muscle defects arise and to find efficacious therapeutic treatments, different animal models have been generated and applied. Among these, simple non-mammalian Drosophila and zebrafish models have proved most useful. This review discusses how zebrafish and Drosophila MD have helped to identify genetic determinants of MDs and design innovative therapeutic strategies with a special focus on DMD, DM1 and congenital MDs."

Fly, mouse, and human cell models of Duchenne muscular dystrophy used to evaluate exon skipping as a potential therapeutic strategy

Gao QQ, Wyatt E, Goldstein JA, LoPresti P, Castillo LM, Gazda A, Petrossian N, Earley JU, Hadhazy M, Barefield DY, Demonbreun AR, Bönnemann C, Wolf M, McNally EM. Reengineering a transmembrane protein to treat muscular dystrophy using exon skipping. J Clin Invest. 2015 Nov 2;125(11):4186-95. PMID: 26457733; PMCID: PMC4639981.

From the abstract: "Exon skipping uses antisense oligonucleotides as a treatment for genetic diseases. ... Exon skipping is currently being tested in humans with dystrophin gene mutations who have Duchenne muscular dystrophy. ... We generated an internally truncated γ-sarcoglycan protein that we have termed Mini-Gamma by deleting a large portion of the extracellular domain. Mini-Gamma provided functional and pathological benefits to correct the loss of γ-sarcoglycan in a Drosophila model, in heterologous cell expression studies, and in transgenic mice lacking γ-sarcoglycan. We generated a cellular model of human muscle disease and showed that multiple exon skipping could be induced in RNA that encodes a mutant human γ-sarcoglycan. Since Mini-Gamma represents removal of 4 of the 7 coding exons in γ-sarcoglycan, this approach provides a viable strategy to treat the majority of patients with γ-sarcoglycan gene mutations."

Review highlights fly research contributions to understanding muscular dystrophies

Plantié E, Migocka-Patrzałek M, Daczewska M, Jagla K. Model Organisms in the Fight against Muscular Dystrophy: Lessons from Drosophila and Zebrafish. Molecules. 2015 Apr 9;20(4):6237-6253. PMID: 25859781.

Table 1 from Plantie et al. Click to view the Open Access review.

From the abstract: "Muscular dystrophies (MD) are a heterogeneous group of genetic disorders that cause muscle weakness, abnormal contractions and muscle wasting, often leading to premature death. ... Structurally, physiologically and biochemically, MDs affect different types of muscles and cause individual symptoms such that genetic and molecular pathways underlying their pathogenesis thus remain poorly understood. To improve our knowledge of how MD-caused muscle defects arise and to find efficacious therapeutic treatments, different animal models have been generated and applied. Among these, simple non-mammalian Drosophila and zebrafish models have proved most useful. This review discusses how zebrafish and Drosophila MD have helped to identify genetic determinants of MDs and design innovative therapeutic strategies with a special focus on DMD, DM1 and congenital MDs."