Prenatal correction of IGF2 to rescue the growth phenotypes in mouse models of Beckwith-Wiedemann and Silver-Russell syndromes.

ABSTRACT: Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are imprinting disorders manifesting as aberrant fetal growth and severe postnatal-growth-related complications. Based on the insulator model, one-third of BWS cases and two-thirds of SRS cases are consistent with misexpression of insulin-like growth factor 2 (IGF2), an important facilitator of fetal growth. We propose that the IGF2-dependent BWS and SRS cases can be identified by prenatal diagnosis and can be prevented by prenatal intervention targeting IGF2. We test this hypothesis using our mouse models of IGF2-dependent BWS and SRS. We find that genetically normalizing IGF2 levels in a double rescue experiment corrects the fetal overgrowth phenotype in the BWS model and the growth retardation in the SRS model. In addit

SUBMITTER: Liao J 

PROVIDER: S-EPMC7968144 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature