OVEREXPRESSION OF IGF-I IN SKELETAL-MUSCLE OF TRANSGENIC MICE DOES NOT PREVENT UNLOADING-INDUCED ATROPHY

This study examined the association between local insulin-like growth factor I (IGF-I) overexpression and atrophy in skeletal muscle. We hyp othesized that endogenous skeletal muscle IGF-I mRNA expression would decrease with hindlimb unloading (HU) in mice, and that transgenic mic e overexpressing human IGF-I (hIGF-I) specifically in skeletal muscle would exhibit less atrophy after HU. Male transgenic mice and nontrans genic mice from the parent strain (FVB) were divided into four groups (n = 10/group): I)transgenic, weight-bearing (IGF-I/WB); 2) transgenic , hindlimb unloaded (IGF-I/HU); 3) nontransgenic, weight-bearing (FVB/ WB); and 4) nontransgenic, hindlimb unloaded (FVB/HU). HU groups were hindlimb unloaded for 14 days. Body mass was reduced (P < 0.05) after HU in both IGF-I (-9%) and FVB mice (-13%). Contrary to our hypothesis , we found that the relative abundance of mRNA for the endogenous rode nt IGF-I (rIGF-I) was unaltered by HU in the gastrocnemius (GAST) musc le Of wild-type FVB mice. High-level expression of hIGF-I peptide and mRNA was confirmed in the CAST and tibialis anterior (TA) muscles of t he transgenic mice. Nevertheless, masses of the GAST and TA muscles we re reduced (P < 0.05) in both FVB/HU and IGF-I/HU groups compared with FVB/WB and IGF-I/WB groups, respectively, and the percent atrophy in mass of these muscles did not differ between FVB and IGF-I mice. There fore, skeletal muscle atrophy may not be associated with a reduction o f endogenous rIGF-I mRNA level in 14-day HU mice. We conclude that hig h local expression of hIGF-I mRNA and peptide in skeletal muscle alone cannot attenuate unloading-induced atrophy of fast-twitch muscle in m ice.