The pro-apoptotic Bax gene modifies susceptibility to craniofacial dysmorphology following gastrulation-stage alcohol exposure.
The pro-apoptotic Bax gene modifies susceptibility to craniofacial dysmorphology following gastrulation-stage alcohol exposure.
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DOI：
10.1002/bdr2.2009
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发表时间：
2022-11-15
影响因子：
2.1
通讯作者：
Parnell, Scott E.
中科院分区：
文献类型：
--
作者：
Fish, Eric W.;Mendoza-Romero, Haley N.;Love, Charlotte A.;Dragicevich, Constance J.;Cannizzo, Michael D.;Boschen, Karen E.;Hepperla, Austin;Simon, Jeremy M.;Parnell, Scott E.
在早期发育过程中，酒精暴露会导致胚胎离散区域的细胞凋亡，这与后期异常的独特模式有关。原肠胚形成发生在人类怀孕的第三周，酒精的目标是外胚层，即眼睛、面部和大脑的前身。这种中线组织缺失导致颅面畸形，如小眼球和平滑人中，这定义了胎儿酒精综合征（FAS）。酒精诱导的细胞死亡的一个重要调节因子是促凋亡蛋白Bax。目前的研究确定了缺乏Bax基因的小鼠是否对原肠胚形成阶段酒精暴露的致病作用不太敏感。雄性和雌性Bax+/−小鼠交配产生具有完全（−/−）或部分（+/−）Bax缺失或Bax+/+野生型对照的胚胎。在妊娠第7天（GD 7），胚胎接受两次酒精（2.9 g/kg，间隔4小时）或对照暴露。12小时后收集一部分胚胎，并检查是否存在凋亡细胞死亡，而其他胚胎在GD 17检查是否存在FAS样面部特征。完整的Bax缺失减少胚胎凋亡细胞死亡和胎儿眼和面部畸形的发生率，表明Bax通常促进酒精诱导的缺陷的发展。对GD 7 Bax+/+和Bax−/−胚胎的RNA-seq分析显示了63个差异表达的基因，其中一些可能与Bax缺失相互作用，以进一步防止细胞凋亡。总之，这些实验确定Bax是原肠胚阶段酒精暴露的主要致畸机制。
During early development, alcohol exposure causes apoptotic cell death in discrete regions of the embryo which are associated with distinctive patterns of later-life abnormalities. In gastrulation, which occurs during the third week of human pregnancy, alcohol targets the ectoderm, the precursor of the eyes, face, and brain. This midline tissue loss leads to the craniofacial dysmorphologies, such as microphthalmia and a smooth philtrum, which define fetal alcohol syndrome (FAS). An important regulator of alcohol-induced cell death is the pro-apoptotic protein Bax. The current study determines if mice lacking the Bax gene are less susceptible to the pathogenic effects of gastrulation-stage alcohol exposure. Male and female Bax+/− mice mated to produce embryos with full (−/−) or partial (+/−) Bax deletions, or Bax+/+ wild-type controls. On gestational day 7 (GD 7), embryos received two alcohol (2.9 g/kg, four hours apart), or control exposures. A subset of embryos was collected 12 hours later and examined for the presence of apoptotic cell death, while others were examined on GD 17 for the presence of FAS-like facial features. Full Bax deletion reduced embryonic apoptotic cell death and the incidence of fetal eye and face malformations, indicating that Bax normally facilitates the development of alcohol-induced defects. An RNA-seq analysis of GD 7 Bax+/+ and Bax−/− embryos revealed 63 differentially expressed genes, some of which may interact with the Bax deletion to further protect against apoptosis. Overall, these experiments identify that Bax is a primary teratogenic mechanism of gastrulation-stage alcohol exposure.
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影响因子：
2.9
作者：
Gilbert, Marcoita T.;Sulik, Kathleen K.;Parnell, Scott E.
通讯作者：
Parnell, Scott E.
影响因子：
2.8
作者：
Anthony, Bruce;Zhou, Feng C.;Ruiz, Joseph
通讯作者：
Ruiz, Joseph
影响因子：
2.9
作者：
ABEL, EL
通讯作者：
ABEL, EL
DOI：
10.1002/tera.1420510102
发表时间：
1995-01-01
期刊：
TERATOLOGY
影响因子：
--
作者：
HOMANICS, GE;MAEDA, N;SULIK, KK
通讯作者：
SULIK, KK
影响因子：
16
作者：
Hoppins S;Edlich F;Cleland MM;Banerjee S;McCaffery JM;Youle RJ;Nunnari J
通讯作者：
Nunnari J