Transactivation of Igf2 in a mouse model of Beckwith-Wiedemann syndrome.
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.
Sun
F L
FL
Laboratory of Developmental Genetics and Imprinting, Department of Development and Genetics, The Babraham Institute, Cambridge, UK.
Dean
W L
WL
Kelsey
G
G
Allen
N D
ND
Reik
W
W
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001506:Beckwith-Wiedemann Syndrome / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D002678:Chimera; D019175:DNA Methylation; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010641:Phenotype; D012097:Repressor Proteins / Q000378:metabolism; D013234:Stem Cells; D015533:Transcriptional Activation
D012097:Repressor Proteins; D007335:Insulin-Like Growth Factor II