Skeletal muscle atrophy can result from a range of physiological conditions, including denervation. To better characterize the molecular genetic events of atrophy, skeletal muscle was isolated from mice following 3 and 14 days of denervation. The gene expression profile of the denervated muscle tissue was analyzed by microarray and compared to control muscle to identify novel atrophy-induced genes. The microarray revealed that Fggy carbohydrate kinase domain containing (Fggy) is expressed in skeletal muscle and is induced in response to denervation. Bioinformatic analysis of the Fggy gene locus revealed two validated alternative isoforms, which we have termed Fggy-001 and Fggy-003. To confirm that Fggy is expressed in muscle cells, the cDNA of the two validated alternative variants was cloned from mouse myoblast cells. Interestingly, a novel alternative splice variant for each of the validated alternative isoforms was also cloned from mouse muscle cells, suggesting at least four Fggy splice variants to be expressed in skeletal muscle. Ectopic expression of Fggy-001 and Fggy-003 resulted in inhibition of muscle cell differentiation and attenuation of the MAP kinase signaling pathway. Finally, confocal fluorescent microscopy analysis revealed that the Fggy-001 transcripts appear to localize to the cytoplasm, while the Fggy-003 transcripts produce a more punctuate localization pattern throughout the cytoplasm of proliferating muscle cells. The characterization of novel genes that are activated during neurogenic atrophy helps improve our understanding of the molecular and cellular events that lead to muscle atrophy and could eventually lead to new therapeutic targets for the treatment of muscle wasting
