GENE-TARGETING AND TRANSGENIC APPROACHES TO IGF AND IGF BINDING-PROTEIN FUNCTION

The ability to manipulate genetic information in the germ line of mice has provided powerful approaches to study gene function in vivo. These approaches have included the establishment of mouse lines in which a specified gene or genes are overexpressed, ectopically expressed, or deleted. Transgenic and gene-targeted mouse lines have been used extensively to study the function of the insulin-like growth factors (IGF), IGF-I and IGF-II, and their receptors and binding proteins. In the IGF system, these technologies have elucidated the roles of the IGFs in fetal and somatic growth and have demonstrated a critical role for this system in transformation and tumorigenesis. Analysis of combinatorial crosses of gene-targeted mouse :lines also has suggested the existence of an as yet unidentified IGF receptor that regulates fetal growth. Similar approaches using transgenic and gene-targeted mouse models have been initiated to study the in vivo functions of the IGF binding proteins. These mouse models provide important tools to test specific functional questions in vivo as well as to study the long term physiological consequences of chronic gene alterations.