Use of transgenic mice for understanding the physiology of insulin-like growth factors

Manipulation of the murine genome, either by the insertion of transgenes or by disruption of native genes (so-called gene knockout, accomplished by homologous recombination), and study of the resultant mutant mice have proved invaluable to our understanding of insulin-like growth factor (IGF) physiology. Such investigations have demonstrated that expression of both IGF-I and IGF-II is essential to normal in utero growth of the fetus, while IGF-II is required for normal placental growth. IGF-I is necessary for normal in utero maturation and postnatal growth. Data from study of type 1 IGF receptor (IGF 1R) knockout mice indicate that this receptor mediates most IGF-I and IGF-II growth-promoting actions. The central importance of the IGFs and the IGF 1R to development is underscored by the fact that IGF 1R knockout mice do not survive past birth. Our more recent studies of transgenic mice have begun to demonstrate IGF-I actions in brain, such as the stimulation of myelination and the augmentation of neurone survival.