Igf1 Conditional Knockout mouse models

Igf1, the mouse ortholog of human IGF1, encodes insulin-like growth factor 1, a 70 amino acid peptide generated by signal and E-peptide processing that is produced largely by hepatocytes under growth hormone control and locally by mesenchymal tissues, circulating almost entirely bound to IGFBP3 and IGFALS in a ternary complex that sets bioavailability. Signaling proceeds through IGF1R and, at higher concentrations, insulin receptor hybrids, activating IRS1 to PI3K and AKT for anabolic growth and the SHC to ERK arm for proliferation. Mice lacking Igf1 show severe intrauterine and postnatal growth failure with substantial, strain-dependent perinatal lethality, so conditional alleles are usually preferable, with hepatocyte deletion isolating endocrine IGF-1 from local production and muscle or osteoblast deletion testing autocrine requirements. Humanized alleles enable evaluation of IGF-1 replacement biologics and neutralizing antibodies. Choose the allele to fit the endpoint, whether longitudinal body composition and bone morphometry, growth hormone axis feedback, or lifespan and tissue growth trajectories.

A floxed Igf1 allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.