Targeted gene mutations define the roles of insulin and IGF-I receptors in mouse embryonic development.
Insulin-like growth factors (IGFs) and their receptors regulate embryonic and post-natal growth. Genetic evidence derived from targeted mouse mutants indicates that both the insulin receptor (IR) and IGF-I receptors (IGF-IRs) are required for mouse embryonic growth. However, the roles of IRs and IGF-IRs are functionally distinct, with IGF-IRs mediating both IGF-I and IGF-II actions, and IRs mediating IGF-II, rather than insulin, action. The combined interactions of IGF-IRs and IRs with IGF-I and IGF-II account for the entirety of the growth effects of these two ligands, and provide the molecular basis for IGFs-mediated intrauterine growth and differentiation. Genetic ablation experiments of insulin receptor substrate-1 (IRS-1) and -2 (IRS-2), two important molecules in the IR and IGF-IR signaling pathways, are also beginning to shed light onto the mechanisms accounting for the specificity of IR and IGF-IR signaling. IRS-1-deficient mice are growth retarded, while IRS-2-deficient mice develop diabetes, indicating that the two molecules play a more specific role than previously recognized in IGF-IR and IR signaling.
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Unit on Genetics and Hormone Action, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Nakae
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Kim
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Park
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Rother
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D000818:Animals; D005314:Embryonic and Fetal Development; D005317:Fetal Growth Retardation / Q000235:genetics; D018390:Gene Targeting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D017526:Receptor, IGF Type 1 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D011972:Receptor, Insulin / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*
D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin