Perinatal lethality in H19 enhancers-Igf2 transgenic mice

The insulin-like growth factor II (IGFII) is a mitogen for a number of cell types in vitro and is required for normal embryonic growth. It has been hypothesized that overexpression of IGF2 is responsible for the increased growth and tumor predisposition in patients with Beckwith-Wiedemann syndrome. Association of increased levels of IGFII with increased growth is also incorporated in a current model for the evolution of Igf2 imprinting. Different experimental approaches to increasing IGFII levels in the mouse have yielded different results with respect to its effects on growth, viability, and tumor development. To investigate the consequences of IGf2 overexpression in the embryonic period, without alterations in the activity of other genes, we produced transgenic mice that express the Igf2 gene under the control of the H19 enhancers. Transgene expression in the embryonic period had no significant effect on the overall size of the embryos, but was associated with perinatal lethality in homozygous, and some heterozygous, mice. A large fraction of homozygous mice also developed a cleft palate. These findings indicate that overexpression of Igf2 can have an adverse effect on viability in the absence of a pronounced effect on overall body growth. The results are consistent with the view that growth and perinatal viability are affected differently by Igf2 overexpression in endodermal and mesodermal tissues.