ID-1 AS A POSSIBLE TRANSCRIPTIONAL MEDIATOR OF MUSCLE DISUSE ATROPHY

Disuse of muscle leads to atrophy of the fibers. This atrophy is corre lated with reduced transcription. We found that when muscle was denerv ated or paralyzed with a nerve impulse block, the mRNA for Id-1, a neg ative regulator of transcription, was increased 2- to 7-fold, To test the effect of high Id-1 levels in active muscles, we made transgenic m ice in which Id-1 was overexpressed under control of regulatory elemen ts which confer tissue- and fiber-type-specific expression in differen tiated muscle cells. Fiber types with high transgene expression were a trophic compared to those in wild-type litter mates, In contrast, fibe r types with low transgene expression displayed hypertrophy, presumabl y caused by an overload due to reduced strength in atrophic synergisti c fibers, Apart from the selective effects on fiber caliber, the muscl e tissue showed no signs of pathology, and apart from a characteristic slightly lower body weight, the transgenic animals looked and behaved normally. We suggest that in the mature muscle, Id-1 may be involved in regulating muscle fiber size at the transcriptional level during di suse.