Role of insulin-like growth factors in embryonic and postnatal growth.
A developmental analysis of growth kinetics in mouse embryos carrying null mutations of the genes encoding insulin-like growth factor I (IGF-I), IGF-II, and the type 1 IGF receptor (IGF1R), alone or in combination, defined the onset of mutational effects leading to growth deficiency and indicated that between embryonic days 11.0 and 12.5, IGF1R serves only the in vivo mitogenic signaling of IGF-II. From E13.5 onward, IGF1R interacts with both IGF-I and IGF-II, while IGF-II recognizes an additional unknown receptor (XR). In contrast with the embryo proper, placental growth is served exclusively by an IGF-II-XR interaction. Additional genetic data suggested that the type 2IGF/mannose 6-phosphate receptor is an unlikely candidate for XR. Postnatal growth curves indicated that surviving Igf-1(-/-) mutants, which are infertile and exhibit delayed bone development, continue to grow with a retarded rate after birth in comparison with wild-type littermates and become 30% of normal weight as adults.
Baker
J
J
Department of Genetics and Development, Columbia University, New York, New York 10032.
Liu
J P
JP
Robertson
E J
EJ
Efstratiadis
A
A
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000502:physiology; D005865:Gestational Age; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains / Q000196:embryology / Q000254:growth & development; D010920:Placenta / Q000502:physiology; D017354:Point Mutation; D011247:Pregnancy; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism
D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1