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:

Igf2 (and Igf2-as)

Chromosome:

Human Chr11p15.5
Mouse Chr7 (distal)

Links:

OMIM  MethDB (Mus musculus)  MethDB (Mus spretus)

Imprinting:

The maternal allele of Igf2 is silenced; paternal allele active in many fetal tissues of mice and humans (DeChiara TM et al, 1991). Some adult tissues show biallelic expression of IGF2, and in humans this loss of the functional imprint may be age-dependent (Issa JP et al, 1996). In fetal and placental cells, Igf2 is imprinted oppositely from the closely linked H19 gene (which see), and these two genes are inversely regulated in cis through shared insulator and enhancer sequences (Bell AC et al, 2000; Hark AT et al, 2000; Leighton PA et al, 1995). Antisense transcripts have been detected in the Igf2 locus; in contrast to several other examples of antisense transcripts within or near imprinted genes, Igf2-as is imprinted in the same direction as Igf2 (Moore T et al, 1997).

Gene Product:

The Igf2 gene encodes the precursor peptide for insulin-like growth factor II (Baker J et al, 1993), and it is expressed in a wide array of mesenchymal and epithelial fetal tissues.

Functional Data:

Insulin like growth factor II is a potent mitogen for fetal and placental cells, and that it also has an anti-apoptotic function (Baker J et al, 1993; Christofori G et al, 1994; Morison IM et al, 1998). A substantial subset of individuals with the Beckwith-Wiedemann overgrowth syndrome (BWS), and related overgrowth phenotypes, show abnormal biallelic expression of IGF2 ("loss of imprinting") in at least some tissues (MacDonald HR et al, 1997; Morison IM et al, 1998; Morison IM et al, 1996; Weksberg R et al, 1993) The tissues that are most affected in BWS coincide with the normal sites of high IGF2 expression (Hedborg F et al, 1994). A mouse model for BWS was constructed by breeding loss of imprinting of Igf2 (an H19 deletion allele) into a p57Kip2-null background (Caspary T et al, 1999). IGF2 loss of imprinting is also a frequent phenomenon in human cancers, including Wilms' tumors and other malignancies associated with BWS (Feinberg AP, 1999; Ogawa O et al, 1993; Rainier S et al, 1993). In Wilms' tumors, this loss of imprinting is invariably linked to silencing and hypermethylation of H19 (Moulton T et al, 1994; Steenman MJ et al, 1994; Taniguchi T et al, 1995); but some BWS tissues can show loss of IGF2 imprinting by an incompletely characterized H19-independent pathway (Engel JR et al, 2000; Brown KW et al, 1996). Germline deletion of Igf2 in mice causes generalized growth retardation, and over-expression of Igf2 causes cellular hyperplasia and tumor susceptibility (Petrik J et al, 1999; Pravtcheva DD et al, 1998; Sun FL et al, 1997)

 

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