Complex contributions of Ets2 to craniofacial and thymus phenotypes of trisomic "Down syndrome" mice.
Complex contributions of Ets2 to craniofacial and thymus phenotypes of trisomic "Down syndrome" mice.
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DOI：
10.1002/ajmg.a.33012
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发表时间：
2009-10
影响因子：
2
通讯作者：
Richtsmeier, Joan T.
中科院分区：
文献类型：
--
作者：
Hill, Cheryl A.;Sussan, Thomas E.;Reeves, Roger H.;Richtsmeier, Joan T.
Ts65Dn小鼠存在人类21号染色体上约一半基因的节段性三体，包括Ets2。这些小鼠的头骨和胸腺发育异常，与唐氏综合症相似。Ets2转录因子基因的过度表达被认为足以在转基因小鼠中产生这些头面部和胸腺缺陷，这些转基因小鼠在混杂启动子下结构性地过度表达处理过的Ets2转录本。对具有不同拷贝数的适当调节的Ets2基因的三体小鼠的评估表明，增加Ets2的剂量不足以对胸腺和Ts65Dn小鼠的大多数颅骨异常产生影响。然而，与Ts65Dn相比，中胚层来源的颅骨元素在Ts65Dn，Ets2+/−中受到的影响明显更大，这表明Ets2相关的过程与中胚层来源的形成组织和神经脊来源的形成组织存在不同的相互作用。我们的结果支持了越来越多的证据表明，多个基因之间的相互作用导致发育紊乱，导致复杂DS表型的变化。
Ts65Dn mice have segmental trisomy for orthologs of about half of the genes on human chromosome 21, including Ets2. These mice develop anomalies of the cranial skeleton and thymus that parallel those in Down syndrome. Over-expression of the Ets2 transcription factor gene was posited to be sufficient to produce these craniofacial and thymus deficits in transgenic mice that constitutively over-express a processed Ets2 transcript under a promiscuous promoter. Evaluation of trisomic mice with varying copy numbers of a properly regulated Ets2 gene indicated increased dosage of Ets2 was not sufficient to produce effects on thymus and most of the cranial anomalies seen in Ts65Dn mice. However, mesoderm-derived cranial skeletal elements are significantly more affected in Ts65Dn, Ets2+/− compared to Ts65Dn littermates suggesting a differential interaction of Ets2-related processes with mesoderm-derived and neural crest-derived formative tissues. Our results support the growing evidence for interactions among multiple genes contributing to developmental perturbations resulting in variation in complex DS phenotypes.
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影响因子：
64.8
作者：
Sussan, Thomas E.;Yang, Annan;Reeves, Roger H.
通讯作者：
Reeves, Roger H.
影响因子：
3.5
作者：
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通讯作者：
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影响因子：
4
作者：
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通讯作者：
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影响因子：
2.6
作者：
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通讯作者：
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影响因子：
8
作者：
Raouf, A;Seth, A
通讯作者：
Seth, A