GENETIC APPROACHES TO THE FUNCTION OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEINS DURING RODENT DEVELOPMENT

Gene targeting provides a direct method for introducing mutations into specific mouse loci. This approach has been used productively to demo nstrate that insulin-like growth factor (IGF) peptides and receptors a re required for normal prenatal growth. Six genes comprising a third m ajor component of the IGF system, the IGF-binding proteins (IGFBPs), a re all expressed during prenatal rodent development. One of these gene s, IGFBP-2, has also been disrupted using gene targeting, and homozygo us null BP-2 mice are characterized by a decreased spleen size and an increase in circulating levels of other IGFBPs. These alterations are less dramatic than initially expected based on the fetal IGFBP-2 expre ssion pattern. These results are discussed in light of both other gene tic ablations involving members of gene families and in the context of the expression of other IGFBPs in rodent fetal and uterine tissues.