Cell
Volume 75, Issue 1, 8 October 1993, Pages 73-82
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Role of insulin-like growth factors in embryonic and postnatal growth

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Summary

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 mutaiional 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 2 IGF/mannose 6-phosphate receptor is an unlikely candidate for XR. Postnatal growth curves indicated that surviving lgf·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.

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Present address: Biological Laboratories, Harvard University, Cambridge, Massachusetts 02138.