Transcriptional disruptions in Down syndrome: a case study in the Ts1Cje mouse cerebellum during post-natal development
Transcriptional disruptions in Down syndrome: a case study in the Ts1Cje mouse cerebellum during post-natal development
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DOI：
10.1111/j.1471-4159.2005.03624.x
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发表时间：
2006-04-01
影响因子：
4.7
通讯作者：
Dauphinot, L
中科院分区：
文献类型：
--
作者：
Potier, MC;Rivals, I;Dauphinot, L
为了了解唐氏综合症的病因和表型严重程度，我们在节段性 16 三体模型 Ts1Cje 小鼠的产后发育过程中寻找大脑（小脑）子结构的转录特征。本研究的目的是调查三体性对发育过程中基因表达变化的影响。在出生时[出生后第 0 天 (P0)]、P15 和 P30 观察到对三重基因的主要基因剂量效应（类似于 1.5）。大约 5% 的非三倍体基因在三体小脑和对照小脑之间表达显着差异，而 25% 的转录组在小脑出生后发育过程中被修改。事实上，三体小脑中分别只有 165、171 和 115 个基因在 P0、P15 和 P30 时失调。令人惊讶的是，在发育过程中以及三体动物中只有三个基因以相似或相反的方向失调。出乎意料的是，这三个基因（Dscr1、Son 和 Hmg14）在 Ts1Cje 模型中出现了三次，并且应该是了解小脑中观察到的表型病因学的候选基因。
To understand the aetiology and the phenotypic severity of Down syndrome, we searched for transcriptional signatures in a substructure of the brain (cerebellum) during post-natal development in a segmental trisomy 16 model, the Ts1Cje mouse. The goal of this study was to investigate the effects of trisomy on changes in gene expression across development time. The primary gene-dosage effect on triplicated genes (similar to 1.5) was observed at birth [post-natal day 0 (P0)], at P15 and P30. About 5% of the non-triplicated genes were significantly differentially expressed between trisomic and control cerebellum, while 25% of the transcriptome was modified during post-natal development of the cerebellum. Indeed, only 165, 171 and 115 genes were dysregulated in trisomic cerebellum at P0, P15 and P30, respectively. Surprisingly, there were only three genes dysregulated in development and in trisomic animals in a similar or opposite direction. These three genes (Dscr1, Son and Hmg14) were, quite unexpectedly, triplicated in the Ts1Cje model and should be candidate genes for understanding the aetiology of the phenotype observed in the cerebellum.