Insulin-like growth factors (IGFs) play important functions in cell proliferation, differentiation and metabolism. The biological actions of IGFs are mediated through binding to the specific receptor-IGF-I receptor. However, in the circulation IGFs are associated with their binding proteins: the insulin-like growth factor binding proteins (IGFBPs). Among the six IGFBPs, IGFBP-3 is the predominant binding protein for IGFs in circulation. IGFBP-3 is believed to play important regulatory roles in the biological actions of IGFs. Although many functions of IGFBP-3 have been described in the last decade, the results were not consistent. The physiological function of IGFBP-3 has not yet been defined. To study the physiological function of IGFBP-3, gene targeting technique was employed to generate a null IGFBP-3 mouse model. The mouse IGFBP-3 gene was obtained by screening a mouse genomic library using a full lengt human IGFBP-3 cDNA. The mouse IGFBP-3 gene restriction map was established by restriction analysis of the mouse IGFBP-3 gene by using different fragments of human IGFBP-3 cDNA as probes. (Abstract shortened by UMI.)