Placentation defects are highly prevalent in embryonic lethal mouse mutants.
Placentation defects are highly prevalent in embryonic lethal mouse mutants.
复制标题
DOI：
10.1038/nature26002
复制
发表时间：
2018-03-22
期刊：
影响因子：
64.8
通讯作者：
Hemberger M
中科院分区：
文献类型：
--
作者：
Perez-Garcia V;Fineberg E;Wilson R;Murray A;Mazzeo CI;Tudor C;Sienerth A;White JK;Tuck E;Ryder EJ;Gleeson D;Siragher E;Wardle-Jones H;Staudt N;Wali N;Collins J;Geyer S;Busch-Nentwich EM;Galli A;Smith JC;Robertson E;Adams DJ;Weninger WJ;Mohun T;Hemberger M
大规模表型分析工作表明，大约 25-30% 的小鼠基因敲除会导致子宫内致死。对这些突变体的分析主要集中在胚胎而不是胎盘，尽管这种胚胎外器官对于发育进程起着关键作用。在这里，我们从破译发育障碍机制计划 (https://dmdd.org.uk) 中筛选了 103 个胚胎致死和亚存活小鼠敲除系的胎盘表型。 68% 在妊娠中期或妊娠中期后致命的品系表现出胎盘畸形。早期致死率（E9.5-E14.5）几乎总是与严重胎盘畸形有关。胎盘缺陷与大脑、心脏和血管发育异常密切相关。对突变滋养层干细胞和条件性敲除的分析表明，滋养层中的主要基因功能涉及大量因素，这些因素在消除时会导致胚胎致死。我们的数据强调了胎盘缺陷在导致胚胎发育异常方面的重要性被严重低估，并提出了控制胎盘形成的关键分子节点。
Large-scale phenotyping efforts have demonstrated that approximately 25-30% of mouse gene knockouts cause intra-uterine lethality. Analysis of these mutants has largely focussed on the embryo but not the placenta, despite the critical role of this extra-embryonic organ for developmental progression. Here, we screened 103 embryonic lethal and subviable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders programme (https://dmdd.org.uk) for placental phenotypes. 68% of lines that are lethal at or after mid-gestation exhibited placental dys-morphologies. Early lethality (E9.5-E14.5) is almost always associated with severe placental malformations. Placental defects strongly correlate with abnormal brain, heart and vascular development. Analysis of mutant trophoblast stem cells and conditional knockouts suggests primary gene function in trophoblast for a significant number of factors that cause embryonic lethality when ablated. Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes governing placentation.
登录
查看更多内容
影响因子：
9.8
作者：
Acuna-Hidalgo, Rocio;Schanze, Denny;Zenker, Martin
通讯作者：
Zenker, Martin
影响因子：
2.1
作者：
Fu, Jinhua;Zhao, Long;Zhu, Xiaohe
通讯作者：
Zhu, Xiaohe
影响因子：
2.6
作者：
Hayashi, Shigemi;Lewis, Paula;McMahon, Andrew P.
通讯作者：
McMahon, Andrew P.
影响因子：
64.8
作者：
Dickinson ME;Flenniken AM;Ji X;Teboul L;Wong MD;White JK;Meehan TF;Weninger WJ;Westerberg H;Adissu H;Baker CN;Bower L;Brown JM;Caddle LB;Chiani F;Clary D;Cleak J;Daly MJ;Denegre JM;Doe B;Dolan ME;Edie SM;Fuchs H;Gailus-Durner V;Galli A;Gambadoro A;Gallegos J;Guo S;Horner NR;Hsu CW;Johnson SJ;Kalaga S;Keith LC;Lanoue L;Lawson TN;Lek M;Mark M;Marschall S;Mason J;McElwee ML;Newbigging S;Nutter LM;Peterson KA;Ramirez-Solis R;Rowland DJ;Ryder E;Samocha KE;Seavitt JR;Selloum M;Szoke-Kovacs Z;Tamura M;Trainor AG;Tudose I;Wakana S;Warren J;Wendling O;West DB;Wong L;Yoshiki A;International Mouse Phenotyping Consortium;Jackson Laboratory;Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS);Charles River Laboratories;MRC Harwell;Toronto Centre for Phenogenomics;Wellcome Trust Sanger Institute;RIKEN BioResource Center;MacArthur DG;Tocchini-Valentini GP;Gao X;Flicek P;Bradley A;Skarnes WC;Justice MJ;Parkinson HE;Moore M;Wells S;Braun RE;Svenson KL;de Angelis MH;Herault Y;Mohun T;Mallon AM;Henkelman RM;Brown SD;Adams DJ;Lloyd KC;McKerlie C;Beaudet AL;Bućan M;Murray SA
通讯作者：
Murray SA
影响因子：
2.7
作者：
Kozak, KR;Abbott, B;Hankinson, O
通讯作者：
Hankinson, O