APPS November 2002 Meeting Abstract 124

The growth factor Insulin-like growth factor-1 (IGF-1) plays a central role in muscle growth, hypertrophy and atrophy¹. The atrophic processes in old skeletal muscle are similar to those occurring in muscles following disuse or denervation, the latter situation being the most severe. Extensive data suggest that administration of IGF-1 can prevent the loss of skeletal muscle mass and function in denervated and ageing muscles. Transgenic mice carrying the mIGF-I transgene driven by the myosin light chain (MLC) promoter exhibit a pronounced skeletal muscle hypertrophy mainly due to the increased cross sectional area of the fast type IIB myofibres^2,3. These transgenic MLC/mIGF-1 mice and another transgenic strain (α-actin/hrIGF-1) over-expressing IGF-1 were used to assess the effects of IGF-1 on many aspects of skeletal muscle biology in normal and dystrophic mdx mice. (A) We hypothesized that IGF-1 would prevent atrophy of myofibres following denervation and found that IGF-I over-expression reduced the atrophy of myofibres in TA muscle of MLC/mIGF-I transgenic mice by up to 30%. (B) To test the proposed beneficial effects of IGF-I over-expression on ageing muscles (and associated denervation), muscles and nerves were analysed morphologically from transgenic (both lines) and control mice at around 14 and 24 months of age. (C) Studies were also carried out in young (2-4 week old) dystrophic mdx/MLC/IGF-I mice to specifically test the hypothesis that IGF-I over-expression can protect dystrophic muscle from damage.