Disruption of the imprinted Grb10 gene leads to disproportionate overgrowth by an Igf2-independent mechanism.

ABSTRACT: To investigate the function of the Grb10 adapter protein, we have generated mice in which the Grb10 gene was disrupted by a gene-trap insertion. Our experiments confirm that Grb10 is subject to genomic imprinting with the majority of Grb10 expression arising from the maternally inherited allele. Consistent with this, disruption of the maternal allele results in overgrowth of both the embryo and placenta such that mutant mice are at birth approximately 30% larger than normal. This observation establishes that Grb10 is a potent growth inhibitor. In humans, GRB10 is located at chromosome 7p11.2-p12 and has been associated with Silver-Russell syndrome, in which approximately 10% of those affected inherit both copies of chromosome 7 from their mother. Our results indicate that changes in GRB10

SUBMITTER: Charalambous M 

PROVIDER: S-EPMC166222 | biostudies-literature | 2003 Jul

REPOSITORIES: biostudies-literature