Maternal transmission of an Igf2r domain 11: IGF2 binding mutant allele (Igf2r^I1565A) results in partial lethality, overgrowth and intestinal adenoma progression.

ABSTRACT: The cation-independent mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R or IGF2R) traffics IGF2 and M6P ligands between pre-lysosomal and extra-cellular compartments. Specific IGF2 and M6P high-affinity binding occurs via domain-11 and domains-3-5-9, respectively. Mammalian maternal Igf2r allele expression exceeds the paternal allele due to imprinting (silencing). Igf2r null-allele maternal transmission results in placenta and heart over-growth and perinatal lethality (>90%) due to raised extra-cellular IGF2 secondary to impaired ligand clearance. It remains unknown if the phenotype is due to either ligand alone, or to both ligands. Here, we evaluate Igf2r specific loss-of-function of the domain-11 IGF2 binding site by replacing isoleucine with alanine in the CD loop (e

SUBMITTER: Hughes J 

PROVIDER: S-EPMC6684648 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature