The sequencing of the human genome showed that there are only about 40 000 genes. However, there are many more proteins. This is because some genes are spliced to produce different protein/peptides which usually have different biological functions. Combining physiological and molecular biology methods made it possible for our team to identify and characterise a local muscle growth/repair factor (MGF). This we found is derived from the insulin-like growth factor I (IGF-I) gene by alternative splicing, but, owing to a reading frame shift, MGF has a unique C-terminal peptide. After resistance exercise, the IGF-I gene is spliced towards MGF which “kick starts” hypertrophy and repair of local muscle damage by activating the muscle stem cells as well as anabolic processes. Interestingly, loss of muscle mass in old age and in certain diseases is associated with an impaired ability to express MGF. In these conditions it seems that the muscle stem (satellite) cell pool is not adequately replenished.

CLONING OF MGF AND OTHER HUMAN MUSCLE IGF-I SPLICE VARIANTS

For some time it has been apparent that muscle mass and strength must be under the control of local growth factors because if one exercises a particular muscle, it is that muscle and not all the muscles of the body that undergo hypertrophy. A little over 10 years ago, our group set out to clone the factor(s) that are involved in autocrine regulation of muscle mass. For this purpose we needed to have an animal model in which we could make muscle grow rapidly. Previous work had shown that the tibialis anterior muscle in the mature rabbit, when held in the stretched position by plaster cast immobilisation combined with low voltage electrical stimulation, increased in mass by 35% in just over a week.¹ It …