Fetal growth restriction in a genetic model of sporadic Beckwith-Wiedemann syndrome.
Fetal growth restriction in a genetic model of sporadic Beckwith-Wiedemann syndrome.
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DOI：
10.1242/dmm.035832
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发表时间：
2018-11-16
影响因子：
4.3
通讯作者：
John RM
中科院分区：
文献类型：
--
作者：
Tunster SJ;Van de Pette M;Creeth HDJ;Lefebvre L;John RM
Beckwith-Wiedemann综合征（BWS）是一种复杂的印迹疾病，涉及胎儿过度生长和胎盘肥大，并且与影响人类染色体11p15.5上印迹基因表达的多种遗传和表观遗传突变相关。大多数BWS病例与该区域内印记控制区2（ICR 2）的甲基化丢失有关，该区域在小鼠中调节几个母系表达的印记基因的沉默。在小鼠中模拟这种疾病被Ascl 2的独特胚胎需求所混淆，Ascl 2在小鼠中而不是在人类中印记。为了克服这个问题，我们产生了一种新的模型，其将远端7号染色体等位基因（DelTel 7）的截短与Ascl 2表达的转基因拯救相结合。这种新的模型概括了与BWS相关的胎盘肥大，但没有导致胎儿过度生长。总结：散发性Beckwith-Wiedemann综合征（BWS）的一种新的遗传小鼠模型概括了胎盘肥大，但胎盘缺陷导致妊娠晚期胎儿生长受限，这与人类BWS的胎儿过度生长特征形成对比。
Beckwith–Wiedemann syndrome (BWS) is a complex imprinting disorder involving fetal overgrowth and placentomegaly, and is associated with a variety of genetic and epigenetic mutations affecting the expression of imprinted genes on human chromosome 11p15.5. Most BWS cases are linked to loss of methylation at the imprint control region 2 (ICR2) within this domain, which in mice regulates the silencing of several maternally expressed imprinted genes. Modelling this disorder in mice is confounded by the unique embryonic requirement for Ascl2, which is imprinted in mice but not in humans. To overcome this issue, we generated a novel model combining a truncation of distal chromosome 7 allele (DelTel7) with transgenic rescue of Ascl2 expression. This novel model recapitulated placentomegaly associated with BWS, but did not lead to fetal overgrowth. Summary: A novel genetic mouse model of sporadic Beckwith–Wiedemann syndrome (BWS) recapitulates placentomegaly, but placental defects lead to late gestation fetal growth restriction, which contrasts with the fetal overgrowth characteristic of BWS in humans.
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DOI：
10.1242/dev.030403
发表时间：
2009-06
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Koerner MV;Pauler FM;Huang R;Barlow DP
通讯作者：
Barlow DP
影响因子：
4
作者：
Delaval, K;Feil, R
通讯作者：
Feil, R
影响因子：
3.3
作者：
LO, S;RUSSELL, JC;TAYLOR, AW
通讯作者：
TAYLOR, AW
影响因子：
9.8
作者：
Lee, MP;DeBaun, M;Feinberg, AP
通讯作者：
Feinberg, AP
影响因子：
3.5
作者：
Du, MJ;Beatty, LG;Sadowski, PD
通讯作者：
Sadowski, PD