Olson L E, Richtsmeier J T, Leszl J, Reeves R H
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Science. 2004 Oct 22;306(5696):687-90. doi: 10.1126/science.1098992.
The "Down syndrome critical region" (DSCR) is a chromosome 21 segment purported to contain genes responsible for many features of Down syndrome (DS), including craniofacial dysmorphology. We used chromosome engineering to create mice that were trisomic or monosomic for only the mouse chromosome segment orthologous to the DSCR and assessed dysmorphologies of the craniofacial skeleton that show direct parallels with DS in mice with a larger segmental trisomy. The DSCR genes were not sufficient and were largely not necessary to produce the facial phenotype. These results refute specific predictions of the prevailing hypothesis of gene action in DS.
“唐氏综合征关键区域”（DSCR）是21号染色体上的一个片段，据称该区域包含导致唐氏综合征（DS）诸多特征的基因，包括颅面畸形。我们利用染色体工程技术培育出仅对与DSCR直系同源的小鼠染色体片段三体或单体的小鼠，并评估了颅面骨骼的畸形情况，这些畸形在具有更大片段三体的小鼠中与DS表现出直接相似性。DSCR基因并不足以导致面部表型，而且在很大程度上也不是产生面部表型所必需的。这些结果驳斥了关于DS中基因作用的主流假说的具体预测。
