International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 32 - COORDINATION OF GROWTH AND METABOLISM BY THE IMPRINTED GRB10 GENE

Ward A, Koumanov F, Charalambous M, Garfield A, Allsop JE, Moorwood K, Smith FM

University of Bath, Bath, United Kingdom

The growth factor receptor-bound protein 10 (Grb10) gene acts as a potent inhibitor of both fetal and placental growth during embryogenesis. Grb10 encodes a signalling adaptor protein that can bind to a number of receptor tyrosine kinases, including the insulin-like growth factor type 1 (Igf1r) and insulin (Insr) receptors. Here, we address the physiological relevance of these biochemical interactions. Genetic tests indicate that the effects of Grb10 on growth are essentially independent of IGF signalling. On the other hand, Grb10 interacts with Insr to control growth during embryogenesis in a highly organ-specific manner and, post-natally, to modulate glucose homeostasis.  Thus, Grb10 appears to fulfil a role in coordinating growth with energy supply.

Grb10 is in most tissues predominantly, but not exclusively, expressed from the maternal allele and therefore behaves in a manner consistent with the parent-offspring conflict hypothesis (briefly, that paternally expressed genes will promote growth and exploit maternal resources opportunistically, while maternally expressed genes will counter this by being growth inhibitory).  However, there is in some tissues a striking reversal of this pattern such that expression occurs exclusively from the paternal allele. The reciprocal imprinting of a single gene with a strong growth-regulatory function will be discussed in relation to the parent-offspring conflict hypothesis.

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