Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome
Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome
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DOI：
10.1093/hmg/ddh154
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发表时间：
2004-07-01
影响因子：
3.5
通讯作者：
Yamakawa, K
中科院分区：
文献类型：
--
作者：
Amano, K;Sago, H;Yamakawa, K
唐氏综合征（DS）是最常见的染色体引起的精神发育迟滞形式，是由21号染色体三体引起的。位于三体区域的基因的过度表达被认为是导致DS表型异常的原因，但这一假设尚未得到充分证实，并且基因剂量效应的存在也受到质疑。因此，我们研究了全球基因表达谱Ts1Cje，小鼠模型DS显示学习缺陷，并有一个节段性三体性染色体16 orthophrenia人类染色体21的一段跨越从Sod 1 Znf295。DNA微阵列分析6 Ts1Cje和6个正常的同窝（2N）小鼠出生后0天的大脑与探针组约11 300个基因显示，表达的基因的数量和它们的身份在Ts1Cje小鼠几乎是相同的2N小鼠。值得注意的是，在三体区域中的大多数基因的表达水平增加了约1.5倍，并且Ts1Cje小鼠中最持续过度表达的前24个基因都位于三体区域。相比之下，在Ts1Cje和2N小鼠中，其他染色体或染色体16整倍体区域上的基因表达水平基本相同（1.0倍）。这些结果表明，在Ts1Cje的三体区域的基因过表达的剂量依赖性的方式，并牵连在DS的分子发病机制。
Down syndrome (DS) is the most common chromosomally caused form of mental retardation and is caused by trisomy of chromosome 21. The over-expression of genes located on the trisomic region has been assumed to be responsible for the phenotypic abnormalities of DS, but this hypothesis has not been confirmed fully and the very existence of gene dosage effects has been called into question. We have therefore investigated global gene expression profiles in Ts1Cje, a mouse model for DS that displays learning deficits and has a segmental trisomy of chromosome 16 orthologous to a segment of human chromosome 21 spanning from Sod1 to Znf295. DNA microarray analyses of six Ts1Cje and six normal littermate (2N) mouse brains at postnatal day 0 with probe sets representing approximately 11 300 genes revealed that the number of expressed genes and their identities in Ts1Cje mice were almost same in 2N mice. Notably, the expression levels of most genes in the trisomic region were increased similar to1.5-fold, and the top 24 most consistently over-expressed genes in the Ts1Cje mice were all located in the trisomic region. In contrast, the expression levels of genes on other chromosomes or the euploid region of chromosome 16 were largely the same (1.0-fold) in Ts1Cje and 2N mice. These results indicate that the genes in the trisomic region of Ts1Cje are over-expressed in a dosage-dependent manner and are implicated in the molecular pathogenesis of DS.