Genetic analysis of the function and development of the inner ear pigment cells essential for hearing acuity.

对听力敏锐度至关重要的内耳色素细胞的功能和发育进行遗传分析。

• 批准号: 14340236
• 负责人: YAMAMOTO Hiroaki
• 金额: $ 9.47万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14340236/
• 关键词: mouse; coat color mutant; pigment cell; Hearing; cochlea; stria vascularis; in situ hybridization; hearing loss; 内耳色素細胞; サブトラクション; in situハイブリダイゼイション

Little is known about the molecular mechanisms by which melanocytes, developed from neural crest cells, play an essential role in hearing acuity. The aim of this study is to elucidate the gene expression profile of the mouse inner ear affected by differentiation of the inner ear melanocytes and to infer the evolution of this melanocyte-envolved inner ear system. First, we found that inner ear melanocytes produce black melanin irrelevant to the coat color of mice. Next, we made two cDNA libraries prepared from the stria vascularis and its surrounding area of the inner ear obtained from wild type mouse and Mitf^<mi-bw> mutant mouse that shows aberrant pigmentation and hearing loss due to the failure of melanocyte differentiation. Then we obtained a subtraction library between those libraries. Differential screening was also carried out using this subtracted library. Micro array analysis of gene expression in each strain was also performed. Expression of many clones that showed differential expression in these two mouse strains was analyzed using in situ hybridization. Strangely enough, many of clones did not show significant in situ signals in each strain, nor many other clones showed prominent differences in expression between these two strains. Still, there were several clones express differentially and some of them did not express in the melanocytes but in their surrounding tissues. Although we need to analyze the sequence structure of these clones in detail, one putative gene seems to be involved in. stress reaction in melanocytes and another one seems to share a conserved roll with ascidian brain pigment cells that play as sensory organs. Functional analysis of these genes should be very important in future.

黑素细胞是由神经脊细胞发育而来的，人们对其分子机制知之甚少，这些细胞在听力方面起着至关重要的作用。本研究的目的是阐明内耳黑素细胞分化对小鼠内耳基因表达谱的影响，并推测这个黑素细胞包绕的内耳系统的进化。首先，我们发现内耳黑素细胞产生的黑色素与小鼠的毛色无关。接下来，我们从野生型小鼠和因黑素细胞分化失败而表现出异常色素沉着和听力损失的MITF^&lt；mi-bw&gt；突变小鼠的内耳血管纹及其周围区域制备了两个cDNA文库。然后，我们获得了这些文库之间的差减文库。利用该消减文库也进行了差异筛选。同时对各菌株的基因表达进行微阵列分析。用原位杂交分析了在这两个小鼠品系中有差异表达的许多克隆的表达。奇怪的是，许多克隆在每个菌株中都没有显示出显著的原位信号，其他许多克隆在这两个菌株之间的表达也没有显著差异。尽管如此，仍有几个克隆差异表达，其中一些克隆不在黑素细胞中表达，而是在其周围组织中表达。虽然我们需要详细分析这些克隆的序列结构，但似乎有一个假定的基因参与了这一过程。黑素细胞的应激反应和另一种似乎与海鞘脑色素细胞一样保守，海鞘脑色素细胞扮演着感觉器官的角色。这些基因的功能分析在未来应该是非常重要的。

项目成果

コートカラー「モデル動物の作製と維持」pp498-523(森脇和郎,山村研一,米川博通 共編)

毛色《模型动物的创建与维护》第498-523页（森胁一夫、山村健一、米川弘道合编）

• 发表时间: 2004
• 作者: 山本 博章

山本 博章: "Isolation and developmental expression of tyrosinase family genes in Xenopuslaevis"Pigment Cell Research. 16. 455-462 (2003)

Hiroaki Yamamoto：“爪蟾酪氨酸酶家族基因的分离和发育表达”色素细胞研究。16. 455-462 (2003)。

脊椎動物色素細胞と進化「ゲノムから見た生物の多様性と進化」(五條掘孝編)

脊椎动物色素细胞与进化《从基因组看生物多样性与进化》（堀五条隆主编）

• 发表时间: 2003
• 作者: Kumata;H.;Yamada;J.;Masuda;K.;Takada;H.;Sato;Y.;Fujiwara;K.;山本博章
• 通讯作者: 山本博章

山本博章: "五條堀孝編 ゲノムから見た生物の多様性と進化"シュプリンガー・フェアラーク東京. 222 (2003)

Hiroaki Yamamoto：“从基因组看生物多样性和进化，由 Gojo Hori 编辑”，Springer Verlag Tokyo，222 (2003)。

Evolution of vertebrate pigment cells in Genomics Unveils Diversity and Evolution(T.Gojobori)(Tokyo)

基因组学中脊椎动物色素细胞的进化揭示了多样性和进化（T.Gojobori）（东京）

• 发表时间: 2003
• 作者: Yamamoto;H.
• 通讯作者: H.