The laboratory of Peter Jones at the University of Massachusetts Medical School reports that Drosophila (fruit fly) lines for studying DUX4 and FRG1 overexpression are freely available worldwide from the Bloomington Drosophila Stock center under “Genes of interest for muscular dystrophy.”
The Jones lab writes: “Aberrant expression of the DUX4-fl gene, which encodes a paired homeobox domain transcription factor, is the primary mediator of FSHD pathology, but the mechanism is unknown. This is mainly due to the lack of phenotypic FSHD-like model organisms available. Therefore, we have produced Drosophila UAS transgenic lines to study the molecular function of both DUX4-fl and another FSHD-related candidate gene, FRG1. Human FRG1 is a direct transcriptional target of DUX4-FL, is highly conserved among species, and is important for myogenesis. With a wide variety of GAL4 transgenic lines available from the stock center, we can now induce these two genes in any GAL4 driver tissue to investigate their molecular functions in vivo. Using an eye-specific GAL4 driver, we found that ectopic eye expression of DUX4-FL results in a loss of photoreceptors, thus providing a readily screenable phenotype for genetic interactions. Using a muscle-specific GAL4 driver, we [Jones laboratory] found that overexpression of Drosohila FRG1 in thoracic muscle impairs flight ability, providing an additional FSHD-like model that is readily screenable for enhancers and suppressors of the phenotype. While there are numerous Drosophila models of neuromuscular diseases as well as six of the nine muscular dystrophies, these are the first Drosophila models applicable towards investigating FSHD. These flies should serve as excellent tools to investigate the pathways affected by the pathogenic factors in FSHD, and may provide insight into normal muscle development and FSHD disease mechanisms.”
The FSH Society initially funded the Jones laboratory’s work on this fly model and supports and encourages the widest possible distribution of FSHD cell lines, models and biomaterials among investigators.