Résumé :
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Mice that over-express growth factor-1 IGF-1 in skeletal myofibres develop muscle hypertrophy, however the mechanism of such hypertrophy in vivo has not been established. This study characterized novel strains of normal and dystrophic (mdx) mice that over-express Class 2 IGF-1 Ea isoform driven by the muscle-specific MLC promoter. Total IGF-1 protein was elevated in skeletal muscles, but not in blood, of all transgenic mice to produce muscle hypertrophy. While non-dystrophic transgenic and wild-type muscles and non-transgenic mdx muscles reached adult steady state and maintained the same weight from 3 to 12 months, the mass of mdx/IGF transgenic muscles continued to increase during adulthood. Analysis of IGF-1 mediated signalling in (fed and especially fasted) adult and young mice showed that elevated IGF-1 has a hypertrophic effect only on skeletal muscles in growth situations: during development or regeneration (1). Examination of growth kinetics of Class 2 IGF-1 Ea mice and myostatin null mice showed divergence of body mass only up to about 6 weeks of age, during the main growth phase. It is proposed that growing myofibres have different properties to mature myofibres (of a fixed length) that are in homeostasis (2). Crossing the 2 strains, to generate mice with elevated IGF-1 and lack of myostatin in skeletal muscles, produced hypertrophy beyond the growth phase, manifested by ongoing divergence in growth rates in adult mice e.g body mass doubled to ~60 gm by 8 months of age. These studies emphasise a difference in response of growing compared with adult myofibres, and demonstrate interactions between the IGF-1 and myostatin signalling pathways.(1) Shavlakadze T et al. (2010) A growth stimulus is needed for IGF-1 to induce skeletal muscle hypertrophy. J Cell Science. Mar 15;123(Pt 6):960-71. (2) Grounds MD, Shavlakadze T. (2011) Growing muscle has different sarcolemmal properties from adult muscle: a proposal with scientific and clinical implications Bioessays. Accepted.
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