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Regulation of supply and demand for maternal nutrients in mouse fetal development by imprinted genes

ReferenceS18928
Principal Investigator / Supervisor Professor Wolf Reik
Co-Investigators /
Co-Supervisors		 Dr Miguel Constancia
Institution Babraham Institute
DepartmentEpigenetics
Funding typeResearch
Value (£) 368,984
StatusCompleted
TypeResearch Grant
Start date 01/05/2003
End date 30/04/2007
Duration48 months

Abstract

Imprinted genes in mammals are key regulators of fetal growth and many of them are expressed in the placenta. We have knocked out the paternally expressed placental-specific Igf2 in the mouse and found that it is a major modulator of placental and fetal growth. We propose that placental-specific Igf2 is an important regulator of supply of nutrients to the fetus, whereas fetal Igf2 is a regulator of demand. Other imprinted genes that regulate growth may also operate by a dual effect on supply and demand. Here we propose to test this hypothesis by investigating various knockouts that eliminate or overexpress Igf2 selectively in the placenta or fetus. We will determine the precise effects on placental and fetal growth, examine placental structure, and measure placental transfer of various solutes. Signalling of fetal demand to the placenta will be examined by array analysis. The extension of the hypothesis to other imprinted genes will be tested in a knockout of the maternally expressed Ip1 gene. This work will provide fundamental insights into the regulation of placental and fetal growth, and into its importance for human health. (Joint with grant 18929).

Summary

unavailable
Committee Closed Committee - Animal Sciences (AS)
Research TopicsX – not assigned to a current Research Topic
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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