Salem M, Kenney PB, Rexroad CE 3rd, Yao J. Microarray gene expression analysis in atrophying rainbow trout muscle: a unique nonmammalian muscle degradation model. Physiol Genomics 28: 33-45, 2006. First published August 1, 2006; doi:10.1152/physiolgenomics.00114.2006.-Muscle atrophy is a physiological response to diverse physiological and pathological conditions that trigger muscle deterioration through specific cellular mechanisms. Despite different signals, the biochemical changes in atrophying muscle share many common cascades. Muscle deterioration as a physiological response to the energetic demands of fish vitellogenesis represents a unique model for studying the mechanisms of muscle degradation in non-mammalian animals. A salmonid microarray, containing 16,006 cDNAs, was used to study the transcriptome response to atrophy of fast-switch muscles from gravid rainbow trout compared with sterile fish. Eighty-two unique transcripts were upregulated and 120 transcripts were downregulated in atrophying muscles. Transcripts having gene ontology identifiers were grouped according to their functions. Muscle deterioration was associated with elevated expression of genes involved in the catheptic and collagenase proteolytic pathways; the aerobic production, buffering, and utilization of ATP; and growth arrest; whereas atrophying muscle showed downregulation of genes encoding a serine proteinase inhibitor, enzymes of anaerobic respiration, muscle proteins as well as genes required for RNA and protein biosynthesis/processing. Therefore, gene transcription of the trout muscle atrophy changed in a manner similar to mammalian muscle atrophy. These changes result in an arrest of normal cell growth, protein degradation, and decreased glycolytic cellular respiration that is characteristic of the fast-switch muscle. For the first time, other changes/mechanisms unique to fish were discussed including genes associated with muscle atrophy. atrophy; Oncorhynchus mykiss SEVERAL PHYSIOLOGICAL and pathological conditions can cause muscle atrophy by triggering unique responses through distinct cellular stimuli. Transcriptional mechanisms of muscle wastage are well characterized at the transcriptome level in mammalian models as a response to nutritional restriction (7), fasting, severe diseases, including cancer, renal failure, diabetes (41, 42), and sepsis (42), as well as muscle disuse or denervation (4, 57). Some studies have dealt with fish muscle atrophy at the level of individual genes/mechanisms (46, 51, 58, 60 -62). The molecular basis of mammalian muscle atrophy has received considerable attention in the literature (25,30). Losing muscle mass results from elevated rate of proteolysis and decreased rate of protein synthesis. Despite the significant amount of literature (30,32,42), the specific roles of the proteolytic systems in degrading mammalian muscle still are unclear. Moreover, we recently showed that fish use different muscle degrading proteolytic strategies compared with mammals (58). The ubiquitin-proteasome pathway,...