title: Overexpression of human insulin-like growth factor binding protein-1 in the mouse leads to nephron deficit.
abstract: IGFs and their binding proteins are important regulators of fetal development. We have previously reported that overexpression of the human IGF binding 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 binding protein-1, pups were growth retarded and had a reduced number of nephrons. Even nontransgenic pups born to heterozygous mothers had a nephron reduction, indicating that renal hypoplasia was secondary to fetal growth retardation. When the transgene was expressed only in the fetus, pups had a normal birth weight and the kidney was normal at birth, as indicated by histologic studies. However, a significant reduction in the nephron number was observed at 3 mo of age. Because nephrogenesis continues for a few days after birth in the mouse, this indicated that human IGF binding protein-1 overexpression altered postnatal nephrogenesis. In addition, exogenously added IGF-II, but not IGF-I, was effective in stimulating in vitro nephrogenesis. Together these elements suggest that reduced amounts of circulating IGFs, presumably IGF-II, impair kidney development.
authors.affiliation: INSERM U489, Hôpital Tenon, 75020 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Doublier
authors.forename: K
authors.initials: K
authors.lastname: Amri
authors.forename: D
authors.initials: D
authors.lastname: Seurin
authors.forename: E
authors.initials: E
authors.lastname: Moreau
authors.forename: C
authors.initials: C
authors.lastname: Merlet-Benichou
authors.forename: G E
authors.initials: GE
authors.lastname: Striker
authors.forename: T
authors.initials: T
authors.lastname: Gilbert
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009399:Nephrons / Q000033:anatomy & histology / Q000196:embryology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins