Overexpression of human insulin-like growth factor binding protein-1 in the mouse leads to nephron deficit

IGFs and their binding proteins are important regulators of fetal developme nt. We have previously reported that overexpression of the human IGF bindin g protein-1 in mice is associated with glomerulosclerosis. The aim of this study was to investigate whether, in that model, decreased bioavailability of IGFs also affected nephrogenesis. When the mothers expressed human IGF b inding protein-1, pups were growth retarded and had a reduced number of nep hrons. Even nontransgenic pups born to heterozygous mothers had a nephron r eduction, indicating that renal hypoplasia was secondary to fetal growth re tardation. When the transgene was expressed only in the fetus, pups had a n ormal birth weight and the kidney was normal at birth, as indicated by hist ologic studies. However, a significant reduction in the nephron number was observed at 3 mo of age. Because nephrogenesis continues for a few days aft er birth in the mouse, this indicated that human IGF binding protein-1 over expression altered postnatal nephrogenesis. In addition, exogenously added IGF-II, but not IGF-II was effective in stimulating in vitro nephrogenesis. Together these elements suggest that reduced amounts of circulating IGFs, presumably IGF-II, impair kidney development.