Igf2r Conditional Knockout mouse models

The mouse Igf2r locus, ortholog of human IGF2R, encodes the cation-independent mannose-6-phosphate receptor, a large type I transmembrane protein whose extracytoplasmic repeats bind both mannose-6-phosphate-tagged lysosomal hydrolases, delivered from the trans-Golgi network to endosomes, and IGF-2, which it internalizes for degradation, making it a ligand clearance sink rather than a signaling receptor. In mouse the gene is maternally expressed and imprinted through the intronic Airn noncoding RNA, a regulatory feature absent in humans that must be considered before extrapolating dosage effects. Maternal-allele nulls are lethal with generalized overgrowth and cardiac defects that are rescued by concurrent Igf2 deletion, evidence that the phenotype reflects excess IGF-2 rather than lysosomal misrouting. Conditional alleles therefore matter for postnatal work, while separation-of-function knockins that ablate the IGF-2 binding repeat while preserving hydrolase sorting cleanly split the two activities. Choose endpoints accordingly, including circulating IGF-2, lysosomal enzyme secretion, and cardiac and placental morphometry.

Igf2r 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.