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

Cell Reports

卷:34

Purnima Singh¹  Tie-Bo Zeng²  Ji Liao²  Nicholas Pierce²  Piroska E. Szabó³  Jeffrey R. Mann³  Diana A. Tran³ 

[1] Irell and Manella Graduate School, City of Hope, Duarte, CA 91010, USA;

[2] Center for Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA;

[3] Division of Molecular and Cellular Biology, City of Hope Cancer Center, Duarte, CA 91010, USA;

关键词: IGF2;    genomic imprinting;    imprinting disorder;    Beckwith-Wiedemann syndrome;    Silver-Russell syndrome;    amniotic fluid;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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 addition, we pharmacologically rescue the BWS growth phenotype by reducing IGF2 signaling during late gestation. This animal study encourages clinical investigations to target IGF2 for prenatal diagnosis and prenatal prevention in human BWS and SRS.

【 授权许可】

Unknown