Craniofacial phenotypes in segmentally trisomic mouse models for Down syndrome
Craniofacial phenotypes in segmentally trisomic mouse models for Down syndrome
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DOI：
10.1002/ajmg.10175
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发表时间：
2002-02-01
期刊：
影响因子：
--
通讯作者：
Reeves, RH
中科院分区：
文献类型：
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作者：
Richtsmeier, JT;Zumwalt, A;Reeves, RH
21号染色体三体(Chr 21)对发育有深远的影响，导致一系列被称为唐氏综合症(DS)的表型。独特的头面部表现是所有DS患者的少数共同特征之一。DS患者的特征性面部主要是由于潜在的头面部骨骼发育不良造成的。Ts65Dn小鼠具有节段性三体16，对人类Chr 21上发现的大约一半基因产生剂量不平衡，表现出与DS的头面部畸形直接对应的特殊骨骼畸形。在这里，我们证明了Ts1Cje小鼠，在Ts65Dn中，大约3/4的基因处于剂量不平衡状态，在头面部骨骼中表现出非常相似的异常模式。然而，Ts65Dn小鼠的一个特征，即导致短头畸形的颅顶扩大，在Ts1Cje小鼠中没有看到。这些观察独立地证实，与人类Chr21基因同源的小鼠基因的剂量不平衡在这两个物种中都有相应的影响。Ts1Cje和Ts65Dn小鼠头面部表型的细微差异对于阐明这种非整倍体破坏发育的机制具有重要意义。(C)2001年Wiley-Liss，Inc.
Trisomy for chromosome 21 (Chr 21) has profound effects on development that result in a constellation of phenotypes known as Down syndrome (DS). Distinctive craniofacial manifestations are among the few features common to all individuals with DS. The characteristic face of a person with DS results primarily from maldevelopment of the underlying craniofacial skeleton. The Ts65Dn mouse, which has segmental trisomy 16, producing dosage imbalance for about half the genes found on human Chr 21, exhibits specific skeletal malformations corresponding directly to the craniofacial dysmorphogenesis in DS. Here we demonstrate that Ts1Cje mice, which are at dosage imbalance for about 3/4 of the genes triplicated in Ts65Dn, demonstrate a very similar pattern of anomalies in the craniofacial skeleton. However, one characteristic of Ts65Dn mice, a broadening of the cranial vault contributing to brachycephaly, is not seen in Ts1Cje mice. These observations independently confirm that a dosage imbalance for mouse genes orthologous to those on human Chr 21 has corresponding effects in both species. The subtle differences in the craniofacial phenotypes of Ts1Cje and Ts65Dn mice have implications for elucidation of the mechanisms by which this aneuploidy disrupts development. (C) 2001 Wiley-Liss, Inc.