TRANSACTIVATION OF IGF2 IN A MOUSE MODEL OF BECKWITH-WIEDEMANN-SYNDROME

The gene IGF2, which encodes a fetal insulin-like growth factor, is im printed, so only one of two parental copies of the gene is expressed, The altered expression of IGF2 has been implicated in Beckwith-Wiedema nn syndrome, a human fetal overgrowth syndrome, which is characterized by overgrowth of several organs and an increased risk of developing c hildhood tumours, We have introduced Igf2 transgenes into the mouse ge nome by using embryonic stern cells, which leads to transactivation of the endogenous Igf2 gene, The consequent overexpression of Igf2 resul ts in most of the symptoms of Beckwith-Wiedemann syndrome, including p renatal overgrowth, polyhydramnios, fetal and neonatal lethality, disp roportionate organ overgrowth including tongue enlargement, and skelet al abnormalities. These phenotypes establish Igf2 overexpression as a key determinant of Beckwith-Wiedemann syndrome.