title: Overexpression of IGF-I in skeletal muscle of transgenic mice does not prevent unloading-induced atrophy.
abstract: This study examined the association between local insulin-like growth factor I (IGF-I) overexpression and atrophy in skeletal muscle. We hypothesized that endogenous skeletal muscle IGF-I mRNA expression would decrease with hindlimb unloading (HU) in mice, and that transgenic mice overexpressing human IGF-I (hIGF-I) specifically in skeletal muscle would exhibit less atrophy after HU. Male transgenic mice and nontransgenic mice from the parent strain (FVB) were divided into four groups (n = 10/group): 1) 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 rodent IGF-I (rIGF-I) was unaltered by HU in the gastrocnemius (GAST) muscle of wild-type FVB mice. High-level expression of hIGF-I peptide and mRNA was confirmed in the GAST and tibialis anterior (TA) muscles of the transgenic mice. Nevertheless, masses of the GAST and TA muscles were 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. Therefore, skeletal muscle atrophy may not be associated with a reduction of endogenous rIGF-I mRNA level in 14-day HU mice. We conclude that high local expression of hIGF-I mRNA and peptide in skeletal muscle alone cannot attenuate unloading-induced atrophy of fast-twitch muscle in mice.
authors.affiliation: Department of Integrative Biology, University of Texas Medical School, Houston, Texas 77030, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Criswell
authors.forename: F W
authors.initials: FW
authors.lastname: Booth
authors.forename: F
authors.initials: F
authors.lastname: DeMayo
authors.forename: R J
authors.initials: RJ
authors.lastname: Schwartz
authors.forename: S E
authors.initials: SE
authors.lastname: Gordon
authors.forename: M L
authors.initials: ML
authors.lastname: Fiorotto
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D001284:Atrophy; D015342:DNA Probes; D019417:Hindlimb Suspension / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D009928:Organ Specificity; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012016:Reference Values; D014158:Transcription, Genetic; D016474:Weight-Bearing / Q000502:physiology*
chemical_list: D000199:Actins; D015342:DNA Probes; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I