Abnormal gene expression in cerebellum of Npc1-/- mice during postnatal development.
Abnormal gene expression in cerebellum of Npc1-/- mice during postnatal development.
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DOI：
10.1016/j.brainres.2010.02.019
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发表时间：
2010-04-14
期刊：
影响因子：
2.9
通讯作者：
Bi, Xiaoning
中科院分区：
文献类型：
--
作者：
Liao, Guanghong;Wen, Zhining;Irizarry, Kristopher;Huang, Ying;Mitsouras, Katherine;Darmani, Mariam;Leon, Terry;Shi, Leming;Bi, Xiaoning
C型尼曼-匹克病是一种常染色体隐性遗传的神经退行性疾病，脂质异常是其主要的细胞病理标志。遗传分析已经在绝大多数病例中鉴定出NPC 1基因突变，而NPC 2基因突变则是导致这些疾病的原因。然而，关于NPC发病机制的细胞机制知之甚少，特别是神经变性，这是通常的死亡原因。为了确定可以解释疾病在最受影响的大脑结构之一中的病理表现的关键步骤，我们使用两种不同的微阵列平台（Agilent和Illumina）在三周龄Npc 1 +/+和Npc 1-/-小鼠的小脑中进行了全局基因表达分析。然后对通过两种微阵列平台鉴定的差异表达基因进行KEGG途径分析。在Npc 1-/-小鼠中，六种途径中的基因表达显著改变;在功能上，这些信号传导途径属于以下三类：1）类固醇和萜类化合物生物合成，2）免疫应答，和3）细胞粘附/运动。此外，Npc 1-/-小鼠中参与脂质转运的几种蛋白质的表达发生了显着改变。我们的研究结果提供了新的分子见解，在NPC疾病的发病机制，并揭示潜在的新的治疗靶点。
Niemann-Pick Type C disease is an autosomal recessive neurodegenerative disorder with abnormal lipid storage as the major cellular pathologic hallmark. Genetic analyses have identified mutations in NPC1 gene in the great majority of cases, while mutations in NPC2 account for the remainders. Yet, little is known regarding the cellular mechanisms responsible for NPC pathogenesis, especially for neurodegeneration, which is the usual cause of death. To identify critical steps that could account for the pathological manifestations of the disease in one of the most affected brain structures, we performed global gene expression analysis in the cerebellum from three-week old Npc1+/+ and Npc1-/- mice with two different microarray platforms (Agilent and Illumina). Differentially-expressed genes identified by both microarray platforms were then subjected to KEGG pathway analysis. Expression of genes in six pathways was significantly altered in Npc1-/- mice; functionally, these signaling pathways belong to the following three categories: 1) steroid and terpenoid biosynthesis, 2) immune response, and 3) cell adhesion/motility. In addition, the expression of several proteins involved in lipid transport was significantly altered in Npc1-/- mice. Our results provide novel molecular insight regarding the mechanisms of pathogenesis in NPC disease and reveal potential new therapeutic targets.
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影响因子：
3.1
作者：
De Windt, Aloys;Rai, Myriam;Laaksonen, Reijo
通讯作者：
Laaksonen, Reijo
影响因子：
46.9
作者：
Canales, Roger D.;Luo, Yuling;Goodsaid, Federico M.
通讯作者：
Goodsaid, Federico M.
影响因子：
4.8
作者：
Cruz, JC;Chang, TY
通讯作者：
Chang, TY
DOI：
10.1093/jnen/64.4.323
发表时间：
2005-04-01
影响因子：
3.2
作者：
Li, H;Repa, JJ;Dietschy, JM
通讯作者：
Dietschy, JM
影响因子：
15.9
作者：
BOYLES, JK;PITAS, RE;TAYLOR, JM
通讯作者：
TAYLOR, JM