Tissue expression patterns identify mouse cilia genes
Tissue expression patterns identify mouse cilia genes
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DOI：
10.1152/physiolgenomics.00128.2007
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发表时间：
2008-01-17
影响因子：
4.6
通讯作者：
Bergman, Daniel A.
中科院分区：
文献类型：
--
作者：
McClintock, Timothy S.;Glasser, Chad E.;Bergman, Daniel A.
在哺乳动物中，纤毛对发育、感觉、细胞信号传导、精子运动和液体运动至关重要。纤毛缺陷是几种先天性综合征的原因，为鉴定纤毛相关基因提供了额外的理由。我们假设在富含高度纤毛细胞的组织中选择性丰富的mrna编码纤毛蛋白。嗅觉上皮、睾丸、表鼻器官、气管和肺中的选择性丰度被证明是一种独特有效的表达模式，可以识别已记录的纤毛相关基因。在鉴定的99个基因中，已知和可疑的纤毛相关基因在统计上被过度代表，但大多数编码功能未知的蛋白质，从而预测新的纤毛相关蛋白质。有证据表明，在高度纤毛细胞嗅觉感觉神经元中，有73个基因存在表达。17个mrna的原位杂交证实了所有17个mrna在嗅觉感觉神经元中的表达。在犁鼻感觉神经元和富含纤毛细胞的邻近组织（如呼吸上皮）中也检测到大多数。其中一种鉴定的蛋白Spa17的免疫反应性与嗅上皮纤毛层的乙酰化微管蛋白共定位。相比之下，纤毛根蛋白Crocc位于离散结构中，其位置与嗅觉感觉神经元的树突旋钮一致。一项预测编码纤毛相关蛋白的小鼠基因的汇编显示，预测基因参与纤毛的研究数量与记录证据之间存在很强的相关性（R = 0.99），这一事实简化了进一步研究纤毛生理学的基因选择。
In mammals, cilia are critical for development, sensation, cell signaling, sperm motility, and fluid movement. Defects in cilia are causes of several congenital syndromes, providing additional reasons to identify cilia-related genes. We hypothesized that mRNAs selectively abundant in tissues rich in highly ciliated cells encode cilia proteins. Selective abundance in olfactory epithelium, testes, vomeronasal organ, trachea, and lung proved to be an expression pattern uniquely effective in identifying documented cilia-related genes. Known and suspected cilia-related genes were statistically overrepresented among the 99 genes identified, but the majority encoded proteins of unknown function, thereby predicting new cilia-related proteins. Evidence of expression in a highly ciliated cell, the olfactory sensory neuron, exists for 73 of the genes. In situ hybridization for 17 mRNAs confirmed expression of all 17 in olfactory sensory neurons. Most were also detected in vomeronasal sensory neurons and in neighboring tissues rich in ciliated cells such as respiratory epithelium. Immunoreactivity for one of the proteins identified, Spa17, colocalized with acetylated tubulin in the cilia layer of the olfactory epithelium. In contrast, the ciliary rootlet protein, Crocc, was located in discrete structures whose position was consistent with the dendritic knobs of the olfactory sensory neurons. A compilation of > 2,000 mouse genes predicted to encode cilia-related proteins revealed a strong correlation (R = 0.99) between the number of studies predicting a gene's involvement in cilia and documented evidence of such involvement, a fact that simplifies the selection of genes for further study of the physiology of cilia.