The detailed entries of the Imprinted Gene Catalogue database were created by Benjamin Tycko, Columbia University, New York and are updated by Ian Morison


 

Detailed entry for Gene:

Igf2r and Igf2r-as/Air

Chromosome:

Human Chr6q26
Mouse Chr17 (proximal)

Links:

OMIM

Imprinting:

Igf2r is strongly imprinted in fetal mouse tissues, with the paternal allele silenced and maternal allele active (Barlow DP et al, 1991), but IGF2R is either weakly imprinted (polymorphic among individuals) or non-imprinted in human tissues (Kalscheuer VM et al, 1993; Oudejans CB et al, 2001; Xu Y et al, 1993). The Igf2r antisense transcript, designated as Igf2r-as/Air, originates from an intron 2 CpG island and is oppositely imprinted from Igf2r. This transcript is necessary for Igf2r imprinting (Wutz A et al, 1997; Steutels F et al, 2002; Sleutels F et al 2003).

Gene Product:

The insulin growth factor 2 receptor: a membrane protein that has a dual role as an Igf2 clearance receptor, which antagonizes Igf2 signaling, and as mannose-6-phosphate receptor, which plays a role in intracellular trafficking by targeting lysosomal enzymes into lysosomes.

Functional Data:

Igf2r binds Igf2 and clears it from the circulation, but does not transmit a growth signal (Baker J et al, 1993). An independent function in intracellular trafficking is to target lysosomal enzymes, which are marked by the mannose-6-phosphate modification, to their destination in the lysosome (Kornfeld S, 1987; Pohlmann R et al, 1995). Igf2r knockout mice show fetal overgrowth and lethality in late gestation (Lau MM et al, 1994; Wang ZQ et al, 1994). Conversely, biallelic expression of Igf2r, engineered by deleting a repressive DNA element from the paternal allele, caused fetal growth retardation (Wutz A et al, 2001). Fetal and placental overgrowth is often observed in cloned mammals, and one study has shown altered methylation and decreased expression of the Igf2r gene after in vitro culture of sheep embryos (Young LE et al, 2001). Igf2r has been proposed as a (non-imprinted) tumor suppressor gene in animal models and in humans, for example see Kong FM et al, 2000; Leboulleux S et al, 2001; Yamada T et al, 1997.

 

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