Insr Conditional Knockout mouse models

Insr, the mouse ortholog of human INSR, encodes a disulfide-linked receptor tyrosine kinase assembled as an alpha-beta heterotetramer, with L1, L2, and cysteine-rich ligand-binding modules and a kinase domain whose activation loop tyrosines undergo trans-autophosphorylation on insulin binding, creating NPXY docking sites for Irs1 and Irs2 that route signals into PI3K, Akt, and Foxo1 as well as Shc-dependent Erk activation; exon 11 splicing generates IR-A and IR-B isoforms with different affinities and tissue distributions. Homozygous nulls are born grossly normal but die within days from ketoacidosis, mirroring human Donohue syndrome, so tissue-restricted deletion with Alb-Cre, Ckmm-Cre, Adipoq-Cre, or Ins1-Cre is the standard approach for dissecting organ-specific insulin action. Kinase-dead and NPXY-mutant knockins separate catalysis from scaffolding, and humanization supports analog and bispecific antibody testing. Igf1r is a close paralog that forms hybrid receptors and buffers signaling, so compound alleles are often necessary.

Insr conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.