Genetic analysis of the function and development of pigment cells essential for visual and auditory senses

对视觉和听觉所必需的色素细胞的功能和发育进行遗传分析

• 批准号: 17370001
• 负责人: YAMAMOTO Hiroaki
• 金额: $ 9.92万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17370001/
• 关键词: pigment cell; mouse; inner ear; eye; auditory sense; visual sense; gene expression

Mammalian pigment cells are essential for audio-visual senses. Still, little is known about the molecular mechanisms underlying these senses. The aim of this study is to elucidate especially the rolls of melanocytes developed from the neural crest. Melanocytes migrate from the neural tube to the skin (hair follicle and dermis), eye (choroid) and inner ear (stria vascularis) and so on. The choroid is adjacent to the RPE surrounding the eye. It is well known that RPE cells are essential for visual function. A failure of this function leads to degeneration of the retina, loss of visual function, resulting in blindness, while for the rolls of melanocytes in choroid, it was only reported to have function to protect choroidal blood vessels from light toxicity. As the first stage of our research, we analyzed the electroretinogram (ERG) of two mutant strains (Mitf^<mi-bw>/Mitf^<mi-bw> and Kit^<W-v>/Kit^W), both showing the black-eyed white (coat) phenotype caused by failure of melanocyte development. We recorded the ERGs of these two mutant mouse strains and compared with the normal mouse ERG to ascertain whether mice without neural crest-derived melanocytes have normal visual function or not. We found that both melanocyte-less mutants show increased oscillatory potentials (OPs). This result first suggests that melanocyte-less mice may have abnormal visual senses. On the other hand, we found a new gene expression in the inner ear strongly suggesting a role of inner ear melanocytes as a stress reliever. The gene is glutathioneS-transferase alpha 4 (Gsta4). Gsta4 encodes one of the cytosolic glutathione S-transferases (GSTs) participating in detoxification processes of many tissues. Functional analysis of these lines of researches should be very important in future to elucidate the involvement of pigment cells in the audio-visual senses.

哺乳动物的色素细胞对视听感官至关重要。然而，人们对这些感觉背后的分子机制知之甚少。本研究的目的是阐明特别是黑素细胞从神经嵴发育的卷。黑素细胞从神经管迁移到皮肤（毛囊和真皮层）、眼睛（脉络膜）和内耳（血管纹）等。脉络膜与眼睛周围的RPE相邻。众所周知，RPE细胞对视觉功能至关重要。这种功能的失败会导致视网膜退化，视觉功能丧失，导致失明，而对于脉络膜中的黑素细胞卷，据报道仅具有保护脉络膜血管免受光毒性的功能。作为我们研究的第一阶段，我们分析了两个突变株（Mitf^<mi-bw>/Mitf^<mi-bw>和Kit^<W-v>/Kit^W）的视网膜电图（ERG），它们都显示了由黑素细胞发育失败引起的黑眼白色（被毛）表型。我们记录了这两种突变小鼠的ERG，并与正常小鼠的ERG进行了比较，以确定没有神经嵴源性黑素细胞的小鼠是否具有正常的视觉功能。我们发现两种缺乏黑色素细胞的突变体都表现出增加的振荡电位（OPs）。这一结果首次表明，缺乏黑素细胞的小鼠可能有异常的视觉感觉。另一方面，我们在内耳中发现了一种新的基因表达，强烈表明内耳黑素细胞具有缓解压力的作用。该基因是谷胱甘肽转移酶- α 4 （Gsta4）。Gsta4编码一种参与许多组织解毒过程的胞质谷胱甘肽s -转移酶（GSTs）。这些研究方向的功能分析对进一步阐明色素细胞在视听感官中的作用具有重要意义。

项目成果

Analysis of the relationship between the mouse inner ear melanocytes, essential for hearing acuity, and anti-oxidant response

分析对听力至关重要的小鼠内耳黑素细胞与抗氧化反应之间的关系

• 发表时间: 2007
• 作者: Uehara;Shigeyuki
• 通讯作者: Shigeyuki

Function of Pigment cells Symposium 2-C1

色素细胞的功能研讨会 2-C1

• 发表时间: 2005
• 作者: Yamamoto;Hiroaki
• 通讯作者: Hiroaki

Structual and functional analysis of melanocytes located in the choroid: A genetic approach

位于脉络膜的黑素细胞的结构和功能分析：遗传方法

• 发表时间: 2007
• 作者: Yano;Yukiko
• 通讯作者: Yukiko

網膜色素上皮の発生を可能にする転写因子Mitfの細胞増殖に関する機能解析

转录因子 Mitf 促进视网膜色素上皮细胞增殖的功能分析

• 发表时间: 2007
• 作者: Yano;Yukiko;築地 長治
• 通讯作者: 築地 長治

色素細胞の多様な機能 シンポジウム2-C1 「感覚シグナルと感覚受容系の進化I:色素細胞・感覚器の機能進化」

色素细胞的多样化功能研讨会2-C1“感觉信号和感觉受体系统的进化I：色素细胞和感觉器官的功能进化”

• 发表时间: 2005
• 作者: Yamamoto;Hiroaki;山本 博章
• 通讯作者: 山本 博章