Transcription profiling of Ts65Dn vs control mice in nine different mouse tissues

To understand the molecular basis of Down syndrome pathogenesis, we performed a transcriptome analysis of nine different tissues in Ts65Dn, an established mouse model of human trisomy 21. Ts65Dn mice have segmental trisomy of mouse chromosome 16 with ca. 128 genes at dosage imbalance (Reeves et al. 1995). The Ts65Dn mouse is widely used as a model for studies of DS because it is at dosage imbalance for the orthologs of about half the 284 Chr21 genes. Ts65Dn mice have several features that directly parallel developmental anomalies of DS. We compare here the expression of 136 mouse orthologs of Chr21 genes, 77 of which are triplicated in Ts65Dn, in trisomic and euploid mice. We designed a mouse cDNA expression array interrogating 136 mmu21 genes. RNA pools from four adult male Ts65Dn mice and four male euploid littermates were prepared from cortex and dissected from three to four month-old mice. Directly labeled first strand cDNA probes from nine different tissues were hybridized to the arrays in replicated hybridizations. A total of 446 genes that are not triplicated in Ts65Dn mice served as controls. These included 62 mmu21 genes from MMU10, MMU17, and non-triplicated portions of MMU16, plus 384 randomly distributed mouse cDNAs from the Unigene collection.为阐明唐氏综合征（Down syndrome, DS）发病的分子机制，我们对Ts65Dn——一种已被广泛验证的人类21三体综合征小鼠模型——的9种不同组织开展了转录组分析。Ts65Dn小鼠携带小鼠16号染色体的节段性三体，约128个基因存在剂量失衡（Reeves等，1995）。由于该模型涵盖了284个人类21号染色体（Chr21）基因中约半数的同源基因且存在剂量失衡，因此被广泛用作唐氏综合征研究的动物模型。Ts65Dn小鼠具备多项与唐氏综合征发育异常直接对应的表型特征。本研究对比了三体与整倍体小鼠中136个人类21号染色体基因的小鼠同源基因的表达情况，其中77个基因在Ts65Dn小鼠中呈三体状态。 我们设计了一款靶向136个小鼠21号染色体同源基因（mmu21）的cDNA表达阵列。从3至4月龄的小鼠中解剖获取皮层组织，随后制备4只成年雄性Ts65Dn小鼠与4只雄性整倍体同窝小鼠的RNA混合样本。针对9种不同组织制备的直接标记第一链cDNA探针，与芯片开展重复杂交实验。本研究共纳入446个未在Ts65Dn小鼠中发生三体的基因作为对照：这些基因包括来自MMU10、MMU17以及MMU16非三体区段的62个mmu21基因，外加Unigene数据库中随机分布的384个小鼠cDNA克隆。