Microarray Analysis of Differentially Expressed Genes in the Brains of Tubby Mice
Microarray Analysis of Differentially Expressed Genes in the Brains of Tubby Mice
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DOI：
10.4196/kjpp.2009.13.2.91
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发表时间：
2009-04-01
影响因子：
2
通讯作者：
Ahn, Young Soo
中科院分区：
文献类型：
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作者：
Lee, Jeong Ho;Kim, Chul Hoon;Ahn, Young Soo
矮胖小鼠的特征是进行性视网膜和耳蜗变性以及迟发性肥胖。这些表型是由 tube 基因的功能丧失突变引起的，并且与多种人类综合征共有，表明 tubeby 蛋白在中枢神经系统 (CNS) 功能中的重要性。尽管有证据表明，Tubby 可能作为介导 G 蛋白偶联受体 (GPCR) 信号传导的转录因子，但 Tubby 调节的任何下游基因尚未确定。为了探索矮胖小鼠大脑中具有区域特异性转录模式的潜在靶基因，我们使用矮胖小鼠的大脑皮层和下丘脑进行了微阵列分析。我们还使用实时 RT-PCR 验证了通过微阵列分析观察到的基因表达水平的变化。我们发现，在胖子小鼠的大脑皮层中，红细胞分化因子 1 (Erdr1) 和 caspase 1 (Casp1) 的表达增加，而 p21 激活激酶 1 (Pak1) 和胆囊收缩素 2 受体 (Cck2r) 的表达减少。在下丘脑区域，Casp 1 上调，μ-晶状体蛋白 (CRYM) 下调。根据已报道的差异表达基因的功能，这些个体或分组基因可能解释了矮胖小鼠的表型。我们讨论了如何将胖子小鼠基因表达的改变理解为胖子表型背后的潜在机制。
The tubby mouse is characterized by progressive retinal and cochlear degeneration and late-onset obesity. These phenotypes are caused by a loss-of-function mutation in the tub gene and are shared with several human syndromes, suggesting the importance of tubby protein in central nervous system (CNS) functioning. Although evidence suggests that tubby may act as a transcription factor mediating G-protein coupled receptor (GPCR) signaling, any downstream gene regulated by tubby has yet to be identified. To explore potential target genes of tubby with region-specific transcription patterns in the brain, we performed a microarray analysis using the cerebral cortex and hypothalamus of tubby mice. We also validated the changes of gene expression level observed with the microarray analysis using real-time RT-PCR. We found that expression of erythroid differentiation factor 1 (Erdr1) and caspase 1 (Casp1) increased, while p21-activated kinase 1 (Pak1) and cholecystokinin 2 receptor (Cck2r) expression decreased in the cerebral cortex of tubby mice. In the hypothalamic region, Casp 1 was up-regulated and mu-crystallin (CRYM) was down-regulated. Based on the reported functions of the differentially expressed genes, these individual or grouped genes may account for the phenotype of tubby mice. We discussed how altered expression of genes in tubby mice might be understood as the underlying mechanism behind tubby phenotypes.