Targeted gene mutations define the roles of insulin and IGF-I receptors in mouse embryonic development

J Pediatr Endocrinol Metab. Jul-Aug 1999;12(4):475-85. doi: 10.1515/jpem.1999.12.4.475.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Embryonic and Fetal Development*
  • Fetal Growth Retardation / genetics
  • Gene Targeting
  • Humans
  • Insulin-Like Growth Factor II / physiology
  • Mice
  • Mice, Knockout
  • Mutation*
  • Receptor, IGF Type 1 / deficiency
  • Receptor, IGF Type 1 / genetics*
  • Receptor, IGF Type 1 / physiology*
  • Receptor, Insulin / deficiency
  • Receptor, Insulin / genetics*
  • Receptor, Insulin / physiology*


  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1
  • Receptor, Insulin