Cell type-specific over-expression of chromosome 21 genes in fibroblasts and fetal hearts with trisomy 21.
Cell type-specific over-expression of chromosome 21 genes in fibroblasts and fetal hearts with trisomy 21.
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DOI：
10.1186/1471-2350-7-24
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发表时间：
2006-03-15
影响因子：
--
通讯作者：
Tycko, B
中科院分区：
文献类型：
--
作者：
Li, CM;Guo, MR;Salas, M;Schupf, N;Silverman, W;Zigman, WB;Husain, S;Warburton, D;Thaker, H;Tycko, B
唐氏综合症（DS）是由21三体（+21）引起的，但这种染色体非整倍体导致的基因表达畸变尚未完全了解。我们使用寡核苷酸微阵列检测了早期和晚期传代对照、+21成纤维细胞和妊娠中期胎儿心脏的mRNA表达。我们用northern blotting、western blotting、实时RT-PCR和免疫组织化学来补充这一分析。我们发现21号染色体基因在+21样本中过度表达的基因中一致地过度代表。然而，这些过表达的基因在三种细胞/组织类型中有所不同。21号染色体基因MX1在衰老+21号成纤维细胞中强烈过表达（平均16倍），通过northern和western blotting证实了这一结果。MX1是干扰素靶基因，其mRNA可被+21成纤维细胞条件培养基中存在的干扰素诱导，提示其过表达存在自分泌环。通过免疫组化，p78MX1蛋白在斑秃病变组织中被诱导，斑秃是一种与退行性变性相关的自身免疫性疾病。我们发现嘌呤生物合成基因GART在+21胎心中强烈过表达（平均3倍），并通过northern blotting和实时RT-PCR验证了这一结果。21号染色体基因的不同亚群在+21的不同细胞类型中过表达，并且对于某些基因，这种过表达是非线性的（>1.5X）。过度活跃的干扰素信号是退行性痴呆中细胞衰老和自身免疫性疾病的候选途径，嘌呤代谢异常在心脏缺陷中的潜在作用有待研究。
Down syndrome (DS) is caused by trisomy 21 (+21), but the aberrations in gene expression resulting from this chromosomal aneuploidy are not yet completely understood. We used oligonucleotide microarrays to survey mRNA expression in early- and late-passage control and +21 fibroblasts and mid-gestation fetal hearts. We supplemented this analysis with northern blotting, western blotting, real-time RT-PCR, and immunohistochemistry. We found chromosome 21 genes consistently over-represented among the genes over-expressed in the +21 samples. However, these sets of over-expressed genes differed across the three cell/tissue types. The chromosome 21 gene MX1 was strongly over-expressed (mean 16-fold) in senescent +21 fibroblasts, a result verified by northern and western blotting. MX1 is an interferon target gene, and its mRNA was induced by interferons present in +21 fibroblast conditioned medium, suggesting an autocrine loop for its over-expression. By immunohistochemistry the p78MX1 protein was induced in lesional tissue of alopecia areata, an autoimmune disorder associated with DS. We found strong over-expression of the purine biosynthesis gene GART (mean 3-fold) in fetal hearts with +21 and verified this result by northern blotting and real-time RT-PCR. Different subsets of chromosome 21 genes are over-expressed in different cell types with +21, and for some genes this over-expression is non-linear (>1.5X). Hyperactive interferon signaling is a candidate pathway for cell senescence and autoimmune disorders in DS, and abnormal purine metabolism should be investigated for a potential role in cardiac defects.
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影响因子：
5.3
作者：
AEBI, M;FAH, J;STAEHELI, P
通讯作者：
STAEHELI, P
影响因子：
5.3
作者：
BRUGGE, KL;GROVE, GL;PIACQUADIO, DJ
通讯作者：
PIACQUADIO, DJ
DOI：
10.1016/0921-8734(91)90013-2
发表时间：
1991-03-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
CARMELIET, G;DAVID, G;CASSIMAN, JJ
通讯作者：
CASSIMAN, JJ
影响因子：
7
作者：
Chrast, R;Scott, HS;Antonarakis, SE
通讯作者：
Antonarakis, SE
DOI：
10.1016/0006-291x(82)90629-5
发表时间：
1982-01-01
影响因子：
3.1
作者：
EPSTEIN, CJ;MCMANUS, NH;BAGLIONI, C
通讯作者：
BAGLIONI, C