组织表达模式可识别小鼠纤毛基因。
Tissue expression patterns identify mouse cilia genes.
作者信息
McClintock Timothy S, Glasser Chad E, Bose Soma C, Bergman Daniel A
机构信息
Department of Physiology, University of Kentucky, Lexington, Kentucky 40536-0298, USA.
出版信息
Physiol Genomics. 2008 Jan 17;32(2):198-206. doi: 10.1152/physiolgenomics.00128.2007. Epub 2007 Oct 30.
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.
在哺乳动物中,纤毛对于发育、感觉、细胞信号传导、精子运动以及液体流动至关重要。纤毛缺陷是多种先天性综合征的病因,这为鉴定与纤毛相关的基因提供了更多理由。我们推测,在富含高度纤毛化细胞的组织中选择性丰富的mRNA编码纤毛蛋白。在嗅觉上皮、睾丸、犁鼻器、气管和肺中的选择性丰富被证明是一种在鉴定已记录的与纤毛相关基因方面独特有效的表达模式。在所鉴定的99个基因中,已知和疑似与纤毛相关的基因在统计学上显著富集,但大多数编码功能未知的蛋白质,从而预测了新的与纤毛相关的蛋白质。73个基因在高度纤毛化的细胞——嗅觉感觉神经元中有表达证据。对17种mRNA进行的原位杂交证实,这17种mRNA在嗅觉感觉神经元中均有表达。大多数还在犁鼻器感觉神经元以及富含纤毛细胞的邻近组织如呼吸道上皮中被检测到。所鉴定的一种蛋白质Spa17的免疫反应性与嗅觉上皮纤毛层中的乙酰化微管蛋白共定位。相比之下,纤毛小根蛋白Crocc位于离散结构中,其位置与嗅觉感觉神经元的树突棘一致。一份超过2000个预测编码与纤毛相关蛋白质的小鼠基因的汇编显示,预测一个基因参与纤毛相关过程的研究数量与该基因参与纤毛相关过程的已记录证据之间存在很强的相关性(R = 0.99),这一事实简化了为进一步研究纤毛生理学而选择基因的过程。