Identification of chicken transmembrane channel-like (TMC) genes: Expression analysis in the cochlea
Identification of chicken transmembrane channel-like (TMC) genes: Expression analysis in the cochlea
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DOI：
10.1016/j.neuroscience.2005.01.046
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Heller, S
中科院分区：
文献类型：
--
作者：
Mutai, H;Mann, S;Heller, S
编码跨膜通道样蛋白（TMC）1的人类基因的突变引起显性和隐性非综合征性听力障碍，这表明该蛋白在内耳中起着重要作用。在这项研究中，我们从耳蜗cDNA文库中克隆了鸡Tmc 2（GgTmc 2），并注释了另外四个TMC家族成员：GgTmc 1、GgTmc 3、GgTmc 6和GgTmc 7。所有鸡TMC具有定义TMC签名基序，并显示其基因组结构的高度保守性时，与其他脊椎动物TMC基因。GgTmc 1位于鸡性染色体Z上的一个位点，该位点与常染色体上哺乳动物直向同源物的位点显示保守的同线性。与此相反，基因座的GgTmc 2不表现出保守的同线性与它的哺乳动物直系同源物。由于小鼠TMC 1和TMC 2在耳蜗毛细胞中限制性表达，我们确定了鸡直系同源物在基底乳头（相当于Corti器官的鸟类）中的表达。虽然GgTmc 2存在于整个基底乳头和其他组织中，但GgTmc 1转录物特异性地在基底乳头的基底部分中检测到，并且在所研究的任何其他组织或器官中检测不到。GgTmc 3和GgTmc 6在分析的所有器官中均可检测到。抗体标记显示，GgTmc 2主要与毛和支持细胞的侧膜。使用分离的细胞通过RT-PCR进一步证实两种细胞类型的GgTmc 2表达。GgTmc 2的这种表达和脑沟细胞定位与这类新型跨膜蛋白在离子转运中的潜在作用一致。(c)2005年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Mutations of the human gene encoding transmembrane channel-like protein (TMC)1 cause dominant and recessive nonsyndromic hearing disorders, suggesting that this protein plays an important role in the inner ear. In this study, we cloned chicken Tmc2 (GgTmc2) from a cochlear cDNA library and we annotated four additional TMC family members: GgTmc1, GgTmc3, GgTmc6, and GgTmc7. All chicken TMCs possess the defining TMC signature motif and display high conservation of their genomic structure when compared with other vertebrate TMC genes. GgTmc1 is localized on the chicken sex chromosome Z at a locus that displays conserved synteny with the loci of mammalian orthologues residing on autosomes. In contrast, the locus of GgTmc2 does not exhibit conserved synteny with its mammalian orthologues. Because murine TMC1 and TMC2 are restrictively expressed in cochlear hair cells, we determined the expression of the chicken orthologues in the basilar papilla, the avian equivalent of the organ of Corti. While GgTmc2 was present throughout the basilar papilla and in other tissues, GgTmc1 transcript was detected specifically in the basal portion of the basilar papilla and was not detectable in any other tissue or organ studied. GgTmc3 and GgTmc6 were detectable in all organs analyzed. Antibody labeling revealed that GgTmc2 is predominantly associated with the lateral membranes of hair and supporting cells. The expression of GgTmc2 by both cell types was further confirmed by RT-PCR using isolated cells. This expression and sulacellular localization of GgTmc2 is in agreement with the proposed potential role of this novel class of transmembrane proteins in ion transport. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.