Gene knockout mice demonstrate that IGF-I is essential for normal muscle development

Insulin like growth factor (IGF-I) is a pleiotropic hormone synthesized by a wide variety of cell types and with effects on a diverse set of target tissues. IGF-I has been implicated in linear growth, glucose metabolism, organ homeostasis and the development and function of the immune and nervous systems. As an approach to the definition of the role of IGF-I in a whole animal we have generated mice with an inactivating mutation in the gene encoding IGF-I. This was accomplished by replacing one endogenous IGF-I allele in embryonic stem cells with a copy that has a neomycin resistance gene inserted into the gene region that encodes the mature IGF-I protein. These es cells were than used to generate mice. Heterozygotes (one normal and one mutant IGF-I allele) are healthy and fertile but are 10-20% smaller than their wild-type littermates. This difference is primarily due to a decreased muscle mass. In contrast, mice which are homozygous for the mutant allele die at birth and are half the weight of their wild-type littermates. The cause of this peri-natal death is being investigated.