Article
Nature 389, 809-815 (23 October 1997) | doi:10.1038/39797; Received 28 May 1997; Accepted 10 September 1997
Transactivation of Igf2 in a mouse model of Beckwith–Wiedemann syndrome
Fang-Lin Sun1,2, Wendy L. Dean1, Gavin Kelsey1, Nicholas D. Allen2 and Wolf Reik1
- Laboratory of Developmental Genetics and Imprinting, Cambridge CB2 4AT, UK
- Laboratory of Developmental Neurobiology, Department of Development and Genetics, The Babraham Institute, Cambridge CB2 4AT, UK
- Present address: Department of Biology, Washington University, Campus Box 1229, St Louis Missouri 63130-4899, USA
Correspondence to: Wolf Reik1 Correspondence and requests for materials should be addressed to W.R. (e-mail: Email: wolf.reik@bbsrc.ac.uk).
Abstract
The gene IGF2, which encodes a fetal insulin-like growth factor, is imprinted, so only one of two parental copies of the gene is expressed. The altered expression of IGF2 has been implicated in Beckwith–Wiedemann syndrome, a human fetal overgrowth syndrome, which is characterized by overgrowth of several organs and an increased risk of developing childhood tumours. We have introduced Igf2 transgenes into the mouse genome by using embryonic stem cells, which leads to transactivation of the endogenous Igf2 gene. The consequent overexpression of Igf2 results in most of the symptoms of Beckwith–Wiedemann syndrome, including prenatal overgrowth, polyhydramnios, fetal and neonatal lethality, disproportionate organ overgrowth including tongue enlargement, and skeletal abnormalities. These phenotypes establish Igf2 overexpression as a key determinant of Beckwith–Wiedemann syndrome.
