Overexpression of insulin-like growth factor binding protein-1 in transgenic mice.

ABSTRACT

Overexpression of insulin-like growth factor-binding protein (IGFBP-1) in transgenic mice has provided insight into the physiological role of this binding protein in modulating the metabolic and growth-promoting effects of the IGFs. IGFBP-1 transgenic mice demonstrate both intrauterine and postnatal growth retardation. Organ weight was proportionately reduced relative to body weight in most organs, with the exception of the brain, which was disproportionately small in transgenic mice. There were no gross neurological manifestations of the reduction in brain size. Transgenic mice also demonstrated fasting hyperglycemia, impaired glucose tolerance, and modest insulin resistance in skeletal muscle and hepatic tissue. From these data, we can conclude that overexpression of IGFBP-1 results in inhibition of IGF action and in profound impairment of brain development, modest inhibition of fetal and postnatal growth, and inhibition of the metabolic effects of the IGFs. Increased expression of IGFBP-1 has been documented in a variety of situations, such as fetal nutritional deprivation and hypoxia, and has been considered to be a marker of metabolic disturbances that cause fetal growth retardation. The observations in IGFBP-1 transgenic mice suggest expression of IGFBP-1 may itself contribute to the growth retardation and impaired fetal brain development.