Prenatal correction of IGF2 to rescue the growth phenotypes in mouse models of Beckwith-Wiedemann and Silver-Russell syndromes.
Prenatal correction of IGF2 to rescue the growth phenotypes in mouse models of Beckwith-Wiedemann and Silver-Russell syndromes.
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DOI：
10.1016/j.celrep.2021.108729
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发表时间：
2021-02-09
期刊：
影响因子：
8.8
通讯作者：
Szabó PE
中科院分区：
文献类型：
--
作者：
Liao J;Zeng TB;Pierce N;Tran DA;Singh P;Mann JR;Szabó PE
beck - wiedemann综合征（BWS）和Silver-Russell综合征（SRS）是一种印迹性疾病，表现为胎儿生长异常和严重的产后生长相关并发症。根据绝缘子模型，三分之一的BWS病例和三分之二的SRS病例与胰岛素样生长因子2 （IGF2）的错误表达一致，IGF2是胎儿生长的重要促进因素。我们建议IGF2依赖性的BWS和SRS病例可以通过产前诊断来识别，并可以通过针对IGF2的产前干预来预防。我们使用igf2依赖性BWS和SRS小鼠模型验证了这一假设。我们发现，在双重拯救实验中，基因正常化IGF2水平纠正了BWS模型中的胎儿过度生长表型和SRS模型中的生长迟缓。此外，我们通过在妊娠后期减少IGF2信号通路，从药理学上挽救了BWS的生长表型。这项动物研究鼓励临床研究将IGF2用于人BWS和SRS的产前诊断和产前预防。Liao等人使用小鼠模型测试了一种产前方法来纠正BWS和SRS两种印记疾病的生长异常。他们发现，胎儿生长因子IGF2被错误调节的情况可以被诊断出来，并且可以通过产前调节IGF2或其信号输出来纠正生长。
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. Liao et al. use mouse models to test a prenatal approach for correcting growth anomalies in two imprinting diseases, BWS and SRS. They find that cases where the fetal growth factor IGF2 is misregulated can be diagnosed, and growth can be corrected by prenatally adjusting IGF2 or its signaling output.
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DOI：
10.1002/ajmg.a.61164
发表时间：
2019-07
期刊：
American journal of medical genetics. Part A
影响因子：
--
作者：
Cohen JL;Duffy KA;Sajorda BJ;Hathaway ER;Gonzalez-Gandolfi CX;Richards-Yutz J;Gunter AT;Ganguly A;Kaplan J;Deardorff MA;Kalish JM
通讯作者：
Kalish JM
影响因子：
30.8
作者：
Engel, N;West, AG;Bartolomei, MS
通讯作者：
Bartolomei, MS
影响因子：
64.5
作者：
BAKER, J;LIU, JP;EFSTRATIADIS, A
通讯作者：
EFSTRATIADIS, A
影响因子：
64.8
作者：
FERGUSONSMITH, AC;SASAKI, H;SURANI, MA
通讯作者：
SURANI, MA
DOI：
10.1016/0167-4781(88)90124-8
发表时间：
1988-09-07
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
DEPAGTERHOLTHUIZEN, P;JANSEN, M;SUSSENBACH, JS
通讯作者：
SUSSENBACH, JS