Fetal overgrowth in the Cdkn1c mouse model of Beckwith-Wiedemann syndrome.
Fetal overgrowth in the Cdkn1c mouse model of Beckwith-Wiedemann syndrome.
复制标题
DOI：
10.1242/dmm.007328
复制
发表时间：
2011-11
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;John RM
印记 CDKN1C 基因的突变与儿童发育障碍贝克威斯-维德曼综合征 (BWS) 有关。多种 Cdkn1c 缺陷小鼠模型重现了 BWS 的某些方面，但没有表现出新生儿过度生长，这是 BWS 患者的一个主要特征。在这项研究中，我们发现 Cdkn1c 突变体在妊娠期间体重增加了 20%，但在妊娠后期，这种正增长轨迹迅速逆转。我们观察到，在生长潜力丧失的同时，胎盘发育受到显着影响，迷路区出现大的血栓病变。将母体血窦与胎儿毛细血管分开的三层滋养层因血窦巨细胞的丢失而紊乱，这表明 Cdkn1c 在维持母胎界面完整性方面发挥着作用。此外，面对日益激烈的宫内竞争，突变幼崽的过度生长有所减少，这确定了 Cdkn1c 在通过胎盘分配母体资源中的作用。这项工作解释了在这种动物模型中精确复制 BWS 的一个困难：多产小鼠（子宫内竞争激烈）和人类（单胎妊娠更常见）之间生殖策略的差异。
Mutations in the imprinted CDKN1C gene are associated with the childhood developmental disorder Beckwith-Wiedemann syndrome (BWS). Multiple mouse models with deficiency of Cdkn1c recapitulate some aspects of BWS but do not exhibit overgrowth of the newborn, a cardinal feature of patients with BWS. In this study, we found that Cdkn1c mutants attained a 20% increase in weight during gestation but experienced a rapid reversal of this positive growth trajectory very late in gestation. We observed a marked effect on placental development concurrently with this loss of growth potential, with the appearance of large thrombotic lesions in the labyrinth zone. The trilaminar trophoblast layer that separates the maternal blood sinusoids from fetal capillaries was disordered with a loss of sinusoidal giant cells, suggesting a role for Cdkn1c in maintaining the integrity of the maternal-fetal interface. Furthermore, the overgrowth of mutant pups decreased in the face of increasing intrauterine competition, identifying a role for Cdkn1c in the allocation of the maternal resources via the placenta. This work explains one difficulty in precisely replicating BWS in this animal model: the differences in reproductive strategies between the multiparous mouse, in which intrauterine competition is high, and humans, in which singleton pregnancies are more common.
登录
查看更多内容
影响因子：
4
作者：
Diaz-Meyer, N;Day, CD;Higgins, MJ
通讯作者：
Higgins, MJ
DOI：
10.1186/1477-7827-2-46
发表时间：
2004-07-05
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Carter, Anthony M;Enders, Allen C
通讯作者：
Enders, Allen C
影响因子：
4
作者：
Engel, JR;Smallwood, A;Maher, ER
通讯作者：
Maher, ER
影响因子：
2.5
作者：
BREIER, G;CLAUSS, M;RISAU, W
通讯作者：
RISAU, W
影响因子：
5.2
作者：
Bliek, Jet;Alders, Marielle;Mannens, Marcel M. A. M.
通讯作者：
Mannens, Marcel M. A. M.