Noting that L-type Ca 2 channels have been implicated in activity-dependent changes in neuronal transcription, Pitri-Rouxel et al.Intramuscular injection óf U7 snRNA chiméras designed tó disrupt 1S pre-mRNA splicing (so as to skip exon 16 and thereby shift the mRNA reading frame) elicited a substantial decrease in unskipped 1S mRNA in mouse tibialis anterior muscle by 2 months after injection.A decrease in 1S protein was apparent 6 months after injection, as well as substantial loss of muscle mass, resulting from a decrease in fiber diameter, and increased fibrosis.Further analysis reveaIed that 1S knockdown led to a decrease in neuronal nitric oxide synthase (nNOS) abundance, accompanied by redistribution of nNOS from the sarcolemma to the cytoplasm, and translocation of the transcription factor FoxO3A to the nucleus (changes consistent with muscle atrophy secondary to inactivity).
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