期刊
CELL REPORTS
卷 34, 期 6, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.108729
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资金
- NIH HHS/United States [R01 GM064378/GM/NIGMS]
BWS and SRS are imprinting disorders related to misexpression of IGF2, and prenatal diagnosis and intervention targeting IGF2 can prevent these conditions. Studies using mouse models demonstrate that normalizing IGF2 levels can correct fetal overgrowth and growth retardation.
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.
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