Development of a model mouse line for hair graying

• Project/Area Number: 23650241
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: Nagoya University (2012-2014); Chubu University (2011)
• Principal Investigator: MASASHI Kato 名古屋大学, 医学(系)研究科(研究院), 教授 (10281073)
• Co-Investigator(Kenkyū-buntansha): TAKEDA Kozue 中部大学, 生命健康科学部, 准教授 (80345884) ; GOTO Yuji 中部大学, 生命健康科学部, 助手 (70362522)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: モデル動物 / 遺伝子改変マウス / 白髪 / メラノサイト / 国際情報交換 / モデルマウス / 加齢 / 発症機構 / 加齢性白髪 / フランス / シンガポール / ドイツ / アメリカ / 疾患モデル動物

Outline of Final Research Achievements

Hair graying is an ordinary disorder for hair pigmentation and a symbol for aging. At present, mechanism of hair graying remains largely unknown, whereas reports for genetically modified mice with changing levels of hair pigmentation are increasing in international scientific journals, according to the recent progression of molecular biology. However, there is very limited report showing model mouse lines for hair graying with aging. We developed original mouse lines for hair graying with aging. In this study, we clarify pathogenesis and molecular mechanism of hair graying in the mice. We also provide the evidence that the mice could be appropriate model mice for hair graying with aging. Moreover, we challenge to develop molecular target therapy for anti-hair graying.

Research Products

• [Journal Article] he effects of non-thermal atmospheric pressure plasma irradiation on expression levels of matrix metalloproteinases in benign melanocytic tumors in RET-transgenic mice (2014)
  • Author(s): Iida M,Yajima I, Ohgami N, Tamura H, Takeda K, Ichihara S, Hori M, Kato M.
  • Journal Title: Eur J Dermatol Volume: 24 Pages: 392-394
  • DOI: 10.1684/ejd.2014.2330
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Non-equilibrium atmospheric pressure plasmas modulate cell cycle-related gene expression levels in melanocytic tumors of RET-transgenic mice. (2014)
  • Author(s): Yajima I, Iida M, Kumasaka MY, Omata Y, Ohgami N, Chang J, Ichihara S, Hori M, Kato M.
  • Journal Title: Exp Dermatol Volume: 23 Pages: 424-425
  • DOI: 10.1111/exd.12415
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An actin-binding protein Espin is a novel growth regulator for melanoma (2014)
  • Author(s): Yanagishita T, Yajima I, Kumasaka MY, Iida M, Xiang L, Tamada Y, Mtsuoto Y, Watabnabe D, Kato M.
  • Journal Title: J Invest Dermatol. Volume: 134 Pages: 2996-2999
  • DOI: 10.1038/jid.2014.249
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Non-thermal atmospheric pressure plasmas as a novel candidate for preventive therapy of melanoma. (2014)
  • Author(s): Omata Y, Iida M, Yajima I, Takeda K, Ohgami N, Masaru Hori H, Kato M.
  • Journal Title: Environ Health Prev Med Volume: 19 Pages: 367-369
  • DOI: 10.1007/s12199-014-0399-1
  • NAID: 50009312844
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Melanoma-Initiating Cells Exploit M2 Macrophage TGF. (2014)
  • Author(s): Tham M, Tan KW, Keeble J, Wang X, Hubert S, Barron L, Tan NS, Kato M, Prevost-Blondel A, Angeli V, Abastado J-P.
  • Journal Title: Oncotarget Volume: 5 Pages: 12027-12042
  • Peer Reviewed / Open Access
• [Journal Article] GNG2 inhibits invasion of human malignant melanoma cells with decreased FAK activity. (2014)
  • Author(s): Yajima I, Kumasaka MY, Yamanoshita O, Zou C, Li X, Ohgami N, Kato M.
  • Journal Title: Am J Cancer Res Volume: 4 Pages: 182-188
  • Peer Reviewed
• [Journal Article] Actin-binding Protein, Espin: a Novel Metastatic Regulator for Melanoma. (2014)
  • Author(s): Yanagishita T, Yajima I, Kumasaka MY, Kawamoto Y, Tsuzuki T, Matsumoto Y, Watanabe D and Kato M.
  • Journal Title: Mol Cancer Res Volume: 12 Pages: 440-446
  • DOI: 10.1158/1541-7786.mcr-13-0468-t
  • Peer Reviewed
• [Journal Article] T-cell mediated immune responses induced in ret transgenic mouse model of malignant melanoma. (2013)
  • Author(s): Abschuetz O, Osen W, Frank K, Kato M, Schadendorf D, Umansky V.
  • Journal Title: Cancers Volume: 4 Pages: 490-503
  • DOI: 10.3390/cancers4020490
  • Peer Reviewed
• [Journal Article] Cyclophosphamide promotes chronic inflammation-dependent immunosuppression and prevents anti-tumor response in melanoma. (2013)
  • Author(s): Sevko A, Sade-Feldman M, Kanterman J, Michels T, Falk C, Ramacher M, Kato M, Schadendorf D, Baniyash M, Umansky V.
  • Journal Title: J Invest Dermatol. Volume: 133 Pages: 1610-1619
  • DOI: 10.1038/jid.2012.444
  • Peer Reviewed
• [Journal Article] Anti-tumor Effect of Paclitaxel is Mediated by Inhibition of MDSCs and Chronic Inflammation in the Spontaneous Melanoma Model. (2013)
  • Author(s): Sevko A, Michels T, Vrohlings M, Umansky L, Beckhove P, Kato M, Shurin GV, Shurin MR, Umansky V.
  • Journal Title: J Immunol Volume: 190 Pages: 2464-2471
  • DOI: 10.4049/jimmunol.1202781
  • Peer Reviewed
• [Journal Article] Inflammatory monocytes are potent anti-tumor effectors controlled by regulatory CD4+ T cells. (2013)
  • Author(s): Pommier A, Delpoux A, Audemard A, Martin B, Douguet L, Lengagne R, Campion AL, Kato M, Avril MF, Auffray C, Lucas B, Prevost-Blondel A.
  • Journal Title: Proc Natl Acad Sci USA Volume: 110 Pages: 13085-13090
  • DOI: 10.1073/pnas.1300314110
  • Peer Reviewed
• [Journal Article] T-cell mediated immune responses induced in ret transgenic mouse model of malignant melanoma. (2013)
  • Author(s): Abschuetz O, Osen W, Frank K, Kato M, Schadendorf D, Umansky V.
  • Journal Title: Cancers Volume: in press
  • Peer Reviewed
• [Journal Article] RAS/RAF/MEK/ERK and PI3K/PTEN/AKT signaling in malignant melanoma progression and therapy. (2012)
  • Author(s): Ya manoshita O Kato M
  • Journal Title: Dermatol. Res. Prac. Volume: 2012 Pages: 1240-1247
  • DOI: 10.1155/2012/354191
  • Peer Reviewed
• [Journal Article] A novel hairless mouse model for malignant melanoma. (2012)
  • Author(s): Thang ND
  • Journal Title: J. Dermatol. Sci. Volume: 10 Pages: 207-12
  • DOI: 10.1016/j.jdermsci.2011.10.010
  • Peer Reviewed
• [Journal Article] Reduced GNG2 expression levels in mouse malignant melanomas and human melanoma cell lines. (2012)
  • Author(s): Yajima I, Kumasaka YM, Naito Y, Yoshikawa T, Takahashi H, Funasaka Y, Suzuki T,Kato M
  • Journal Title: Am J Cancer Res Volume: 2 Pages: 322-329
  • Peer Reviewed
• [Journal Article] Cancer-Induced Immunosuppression: IL-18-Elicited Immunoablative NK Cells. (2012)
  • Author(s): Terme M, Ullrich E, Aymeric L, Meinhardt K, Coudert J, Desbois M, Ghiringhelli F, Viaud S, Ryffel B, Yagita H, Chen L, Mecheri S, Kaplanski G, Prevost-Blondel A, Kato M, Schultze JL, Tartour E, Kroemer G, Degli-Esposti M, Chaput N, Zitvogel L
  • Journal Title: Cancer Res Volume: 72 Pages: 2757-2767
  • DOI: 10.1158/0008-5472.can-11-3379
  • Peer Reviewed
• [Journal Article] Tumor-Expressed Inducible Nitric Oxide Synthase Controls Induction of Functional Myeloid-Derived Suppressor Cells through Modulation of Vascular Endothelial Growth Factor Release. (2012)
  • Author(s): Jayaraman P, Parikh F, Lopez-Rivera E, Hailemichael Y, Clark A, Ma G, Cannan D, Ramacher M, Kato M, Overwijk WW, Chen SH, Umansky VY, Sikora AG.
  • Journal Title: J Immunol Volume: 188 Pages: 5365-5376
  • DOI: 10.4049/jimmunol.1103553
  • Peer Reviewed
• [Journal Article] Functional analysis of GNG2 in human malignant melanoma cells. (2012)
  • Author(s): Yajima I, et al.
  • Journal Title: Journal of Dermatological Science Volume: 68 Pages: 172-178
  • DOI: 10.1016/j.jdermsci.2012.09.009
  • Peer Reviewed
• [Journal Article] Molecular network associated with MITF on skin melanoma development and progression. (2012)
  • Author(s): Ya manoshita O Kato M
  • Journal Title: J. Skin Cancer Volume: 2011 Pages: 1-7
  • DOI: 10.1155/2011/730170
  • Peer Reviewed
• [Journal Article] c-Ret-mediated hearing losses. (2012)
  • Author(s): Ohgami, N., Kato, M（10人中10番目）, et al.
  • Journal Title: Int J Clin Exp Pathol. Volume: 5 Pages: 23-8
  • Peer Reviewed
• [Journal Article] Partial impairment of c-Ret at tyrosine 1062 accelerates age-related hearing loss in mice. (2012)
  • Author(s): Nobutaka Ohgami
  • Journal Title: Neurobiol. Aging Volume: 33
  • DOI: 10.1016/j.neurobiolaging.2011.04.002
  • Peer Reviewed
• [Journal Article] L-cysteine as a regulator for arsenic-mediated cancer-promoting and anti-cancer effects. (2011)
  • Author(s): Kato M, Kumasaka MY, Takeda K, Hossain K, Iida M, et al
  • Journal Title: Toxcol. In Vitro Volume: 25(3) Pages: 623-629
  • DOI: 10.1016/j.tiv.2010.12.012
  • Peer Reviewed
• [Journal Article] Control of Genetically Designed Protein Tyrosine Kinase Activities by Environment-Linked Redox Reactions. (2011)
  • Author(s): Nakashima, I., Kawamoto, Y., Takeda, K., Kato, M.
  • Journal Title: Enzyme Res Volume: 10 Pages: 896567-896567
  • DOI: 10.4061/2011/896567
  • Peer Reviewed
• [Journal Article] BMP-4 down-regulates the expression of Ret in murine melanocyte precursors. (2011)
  • Author(s): Nakajima K, Sano S, Uchida Y, Akiyama M, Morita Y, Shimizu H.
  • Journal Title: J. Dermatol. Sci. Volume: 63(1) Pages: 64-6
  • DOI: 10.1016/j.jdermsci.2011.03.009
  • NAID: 10030891988
  • Peer Reviewed
• [Journal Article] Requirement of endothelin receptor B expressed in spiral ganglion neurons for postnatal development of hearing. (2011)
  • Author(s): Ida-Eto M, Ohgami N, Iida M, et al
  • Journal Title: J. Biol. Chem. Volume: 286(34) Pages: 29621-29626
  • DOI: 10.1074/jbc.m111.236802
  • Peer Reviewed
• [Journal Article] Sunlight exposure-mediated DNA damage in young adults. (2011)
  • Author(s): Kato M, Iida M, et al
  • Journal Title: Cancer Epidemiol. Biomaker Prevent. Volume: 20(8) Pages: 1622-1628
  • DOI: 10.1158/1055-9965.epi-11-0228
  • Peer Reviewed
• [Journal Article] IL-18 induces PD-1-dependent immunosuppression in cancer. (2011)
  • Author(s): Terme M, Ullrich E, Aymeric L, Meinhardt K, Desbois M, Delahaye NF, Viaud S, Ryffel B, Yagita H, Kaplanski G, Prevost-Blondel A, Kato M, Schultze JL, Tartour E, Kroemer G, Chaput N, Zitvogel L
  • Journal Title: Cancer Res. Volume: 71 Pages: 5412-5422
  • DOI: 10.1158/0008-5472.can-11-0993
  • Peer Reviewed
• [Journal Article] Proteomic identification of hippocampal proteins vulnerable to oxidative stress in excitotoxin-induced acute neuronal injury. (2011)
  • Author(s): A. Furukawa, Y. Kawamoto, Y. Chiba, S.Takei, S. Hasegawa-Ishii, N. Kawamura, K. Yoshikawa, M. Hosokawa, S. Oikawa, M. Kato, A. Shimada
  • Journal Title: Neurobiology of Disease Volume: 43 Pages: 706-14
  • DOI: 10.1016/j.nbd.2011.05.024
  • Peer Reviewed
• [Journal Article] Antioxidative effects of cherry leaves extract on tert-butyl hydroperoxide-mediated cytotoxicity through regulation of thioredoxin-2 protein expression level. (2011)
  • Author(s): Taguchi N, Uemura N, Goto Y, Sakura M, Hara K, Niwa M, Iida M, Yanagishita T, Watanabe D, Kato M
  • Journal Title: J. Toxicol. Environ. Health A. Volume: 74 Pages: 1240-7
  • DOI: 10.1080/15287394.2011.570229
  • Peer Reviewed
• [Journal Article] Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. (2011)
  • Author(s): Toh, B., Kato, M（10人中7番目）, et al.
  • Journal Title: PLoS Biol. Volume: 9
  • DOI: 10.1371/journal.pbio.1001162
  • Peer Reviewed
• [Journal Article] Sildenafil exerts anti-tumor effects and reduces Gr1+CD11b+ cell-mediated immunosuppression in ret transgenic mouse melanoma model. (2011)
  • Author(s): Meyer, C., Kato, M（8人中11番目）, et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108 Pages: 17111-6
  • DOI: 10.1073/pnas.1108121108
  • Peer Reviewed
• [Journal Article] Barium promotes anchorage-independent growth and invasion of human HaCaT keratinocytes via activation of c-SRC kinase. (2011)
  • Author(s): Thang, N.D., Kato, M（9人中9番目）, et al.
  • Journal Title: PLoS ONE Volume: 6
  • DOI: 10.1371/journal.pone.0025636
  • Peer Reviewed
• [Journal Article] Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T cell infiltration and tumor control. (2011)
  • Author(s): Hong, M., Kato, M（11人中7番目）, et al.
  • Journal Title: Cancer Res. Volume: 71 Pages: 6997-7009
  • DOI: 10.1158/0008-5472.can-11-1466
  • Peer Reviewed
• [Presentation] Ednrb遺伝子関連メラノーマの予防、治療に有効な遺伝子の探索 (2014)
  • Author(s): 熊坂真由子、矢嶋伊知朗、飯田真知子、神保佳奈、田村青鳥、大神信孝、加藤昌志
  • Organizer: 第84回 日本衛生学会学術総会
  • Place of Presentation: 岡山県岡山市 岡山コンベンションセンター
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] 悪性黒色腫におけるNKX3-1遺伝子変異の解析 (2014)
  • Author(s): 山ノ下 理、玉利裕貴、加藤昌志
  • Organizer: 第84回 日本衛生学会学術総会
  • Place of Presentation: 岡山県岡山市 岡山コンベンションセンター
  • Year and Date: 2014-05-25 – 2014-05-27
• [Presentation] 悪性黒色腫におけるNKX3.1遺伝子変異の解析 (2013)
  • Author(s): 山ノ下理・岡澤泰平・加藤昌志
  • Organizer: 第83回日本衛生学会学術総会
  • Place of Presentation: 金沢市 金沢大学鶴間・宝町キャンパス
• [Presentation] 動物モデルを用いた非熱的大気圧プラズマによる抗腫瘍効果の検討 (2013)
  • Author(s): 飯田真智子、矢嶋伊知朗、中川薫、大神信孝、近藤 博基、竹田圭吾、堀勝、加納 浩之、加藤昌志
  • Organizer: 第83回日本衛生学会学術総会
  • Place of Presentation: 金沢市 金沢大学鶴間・宝町キャンパス
• [Presentation] Analysis of endothelin receptor B expressed in spiral ganglion neurons. (2012)
  • Author(s): 大神信孝、飯田真智子、矢嶋伊知朗、加藤昌志
  • Organizer: 第24回日本色素細胞学会学術大会
  • Place of Presentation: 長浜市 長浜バイオ大学
• [Presentation] 皮膚メラニンと日光曝露による酸化ストレスとの関連 (2012)
  • Author(s): 飯田真智子、矢嶋伊知朗、大神信孝、田巻満里絵、加藤昌志
  • Organizer: 第24回日本色素細胞学会学術大会
  • Place of Presentation: 長浜市 長浜バイオ大学
• [Presentation] メラノーマにおけるGNG2の機能 (2012)
  • Author(s): 矢嶋伊知朗、熊坂真由子、大神信孝、加藤昌志
  • Organizer: 第24回日本色素細胞学会学術大会
  • Place of Presentation: 長浜市 長浜バイオ大学
• [Presentation] Therapeutic effect of non-thermal atmospheric plasma on tumor in vivo (2012)
  • Author(s): Ichiro Yajima, Masashi Kato （7人中7番目）
  • Organizer: 4th International Symposium on Advanced Plasma Science and its Applications for Nitrides and Nanomaterials
  • Place of Presentation: Chubu University, Kasugai, Aichi, Japan
• [Presentation] A redox-linked novel pathway for (2011)
  • Author(s): Masashi Kato
  • Organizer: JSPS AA Science Platform Program in Malaysia
  • Place of Presentation: University Malaysia Sabah, Malaysia
• [Presentation] メラニン制御を可能にする画期的なアンチエイジング剤の開発
  • Author(s): 加藤昌志
  • Organizer: 第2回国際化粧品展
  • Place of Presentation: 東京ビックサイト（東京都江東区）
  • Invited
• [Presentation] 環境を整え、病気を予防する：海外の環境衛生学研究を例として
  • Author(s): 加藤昌志
  • Organizer: 豊秋奨学会国際学生交流会
  • Place of Presentation: ホテル・ナゴヤキャッスル（名古屋市）
  • Invited
• [Remarks] 名古屋大学大学院医学系研究科・医学部医学科
  • URL: http://www.med.nagoya-u.ac.jp/medical/2511/index.html
• [Remarks] 名古屋大学大学院医学系研究科 環境労働衛生学
  • URL: http://www.med.nagoya-u.ac.jp/hygiene/
• [Remarks] 名古屋大学大学院医学系研究科 教員詳細
  • URL: http://profs.provost.nagoya-u.ac.jp/view/html/100001262_ja.html?k=%E5%8A%A0%E8%97%A4%E3%80%80%E6%98%8C%E5%BF%97
• [Remarks] 名古屋大学大学院医学系研究科 環境労働衛生学
  • URL: http://www.med.nagoya-u.ac.jp/hygiene/
• [Remarks]
  • URL: http://www.chubu.ac.jp/about/faculty/profile/588a920fe73a44df04e50c9c3eda630d04e09e86.html
• [Patent(Industrial Property Rights)] 幹細胞を標的とした薬効及び毒性の評価法 (2013)
  • Inventor(s): 飯田真智子、加藤昌志
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-131956
  • Filing Date: 2013-06-24
  • Application Year: 2013
• [Patent(Industrial Property Rights)] 幹細胞を標的とした薬効及び毒性の評価法 (2012)
  • Inventor(s): 飯田真智子、加藤昌志
  • Industrial Property Rights Holder: 中部大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-243119
  • Filing Date: 2012-11-02
  • Application Year: 2012
• [Patent(Industrial Property Rights)] 色素細胞性疾患のモデル動物及びその用途 (2011)
  • Inventor(s): 加藤昌志、飯田真智子
  • Industrial Property Rights Holder: 中部大学
  • Industrial Property Number: 2011-253454
  • Filing Date: 2011
  • Application Year: 2011