Analyses of biological significance of GPI-anchored protein CD109 in mouse development

GPI锚定蛋白CD109在小鼠发育中的生物学意义分析

• 批准号: 21590435
• 负责人: MURAKUMO Yoshiki
• 金额: $ 2.91万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590435/
• 关键词: 疾患モデル動物; CD109; ノックアウトマウス; 表皮ケラチノサイト; 初代培養; STAT3; TGFβ; トランスジェニックマウス; 結合蛋白; 体毛発育異常; 表皮過形成; TGFssシグナル; 免疫組織化学染色; 脱毛; 精子形成

We generated CD109 knockout mouse to assess biological significance of GPI-anchored protein CD109 in mouse development. In wild-type mouse, CD109 expression was detected in basal and suprabasal region of the epidermis and seminiferous tubules of the testis. CD109./. mice could be alive and showed transient hair-loss from postnatal day 7(P7) to P28. CD109./. male and female mice were fertile. Histopathological analyses revealed that epidermal hyperplasia was detected in CD109./. mice from P7 to P70, and ectatic hair follicles were apparent from p14 to p21. Since epidermal hyperplasia was seen in dorsal skin epidermis, which does not have hair and hair follicles, we thought that CD109-deficiency develops epidermal hyperplasia, which leads to ectatic hair follicle and hair-loss. Immunohistochemical analyses revealed that STAT3 phosphorylation was apparently upregulated compaired with wild-type mice, suggesting that STAT3 signaling may be associated with epidermal hyperplasia of CD109./. mice. Next, we tried to detect secreted CD109 and to identify its interaction partners in the serum of CD109 transgenic mice. Secreted CD109 in mouse serum was detected by Western blotting, however, we could not identify candidates of CD109-interaction proteins in this experiment. Then, we attempted to identify CD109-interaction proteins in the medium of CD109-overexpressing culture cells. We successfully identified a candidate of CD109-interaction protein in this experiment, and now we are investigating biological significance of the interaction between CD109 and the interaction protein.

本研究通过构建CD 109基因敲除小鼠模型，探讨GPI锚定蛋白CD 109在小鼠发育中的生物学意义。在野生型小鼠中，在睾丸的表皮和曲细精管的基底和基底上区域检测到CD 109表达。CD109./.小鼠可以存活，并且从出生后第7天（P7）到P28显示出短暂的毛发脱落。CD109./.雄鼠和雌鼠都能生育。组织学分析显示，在CD 109中检测到表皮增生。小鼠从P7到P70，从p14到p21，毛囊扩张明显。由于在背部皮肤表皮中观察到表皮增生，而背部皮肤表皮没有毛发和毛囊，我们认为CD 109缺乏会导致表皮增生，从而导致毛囊扩张和毛发脱落。免疫组织化学分析显示，与野生型小鼠相比，STAT 3磷酸化明显上调，表明STAT 3信号传导可能与CD 109的表皮增生有关。小鼠接下来，我们试图检测分泌的CD 109并鉴定其在CD 109转基因小鼠血清中的相互作用伴侣。通过Western印迹检测小鼠血清中分泌的CD 109，然而，在本实验中，我们不能鉴定CD 109相互作用蛋白的候选者。然后，我们试图在CD 109过表达培养细胞的培养基中鉴定CD 109相互作用蛋白。本实验成功鉴定了一个与CD 109相互作用的候选蛋白，并对该蛋白与CD 109相互作用的生物学意义进行了研究。

项目成果

Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cells.

• DOI: 10.1091/mbc.e10-08-0724
• 发表时间: 2011-03-15
• 期刊: Molecular biology of the cell
• 影响因子: 3.3
• 作者: Matsushita E;Asai N;Enomoto A;Kawamoto Y;Kato T;Mii S;Maeda K;Shibata R;Hattori S;Hagikura M;Takahashi K;Sokabe M;Murakumo Y;Murohara T;Takahashi M
• 通讯作者: Takahashi M

Analysis of glial cell line-derived neurotrophic factor-inducible zinc finger protein 1 expression in human diseased kidney.

• DOI: 10.1016/j.humpath.2010.09.015
• 发表时间: 2011-06
• 期刊: Human pathology
• 影响因子: 3.3
• 作者: Shoji Saito;Y. Murakumo;T. Tsuzuki;Atsushi Dambara;Takuya Kato;A. Enomoto;N. Asai;S. Maruyama;S. Matsuo;Masahide Takahashi

膀胱癌におけるCD109発現の臨床病理学的特徴との関連性の検討

膀胱癌CD109表达与临床病理特征的关系探讨

• 发表时间: 2010
• 作者: 伊藤智広;藤田泰典;伊藤美佳子;増田章男;市原正智;小島俊男;野澤義則;大野欽司;伊藤雅史;伊藤智広;市原正智;祖父江沙矢加;山本純矢;大内靖夫;喬善楼;Murakumo Y;三井伸二;村雲芳樹;萩倉美奈子
• 通讯作者: 萩倉美奈子

GPIアンカー型膜蛋白CD109のヒト腫瘍における発現とその生物学的意義

GPI锚定膜蛋白CD109在人肿瘤中的表达及其生物学意义

• 发表时间: 2009
• 作者: 石川文洋;白橋雅人;円谷健;藤井郁雄;村雲芳樹
• 通讯作者: 村雲芳樹

これからはじめる人のためのバイオ実験基本ガイド

适合刚开始生物实验的人的基本指南

• 发表时间: 2010
• 作者: 村雲芳樹;他3名
• 通讯作者: 他3名