Identification of cells or cell lineage responsible for atopic dermatitis-like skin lesions in model mice for human diseases by means of TRECK method

• Project/Area Number: 14208098
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH
• Principal Investigator: YONEKAWA Hiromichi TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, Vice Director, 東京都臨床医学総合研究所, 参事研究員(副所長) (30142110)
• Co-Investigator(Kenkyū-buntansha): TAYA CHOJI TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, Senior Researcher, 東京都臨床医学総合研究所, 研究員 (90175456) ; MATSUOKA KUNIE TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, Researcher, 東京都臨床医学総合研究所, 研究員 (40291158) ; KOHNO KENJI NARA INSTITUTE OF SCIENCE AND TECHNOLOGY, RESEARCH AND EDUCATION CENTER FOR GENETIC INFORMATION, Professor, 遺伝子教育研究センター, 教授 (50142005) ; KARASUYAMA HAJIME TOKYO MEDICAL AND DENTAL UNIVERSITY, DEPARTMENT OF IMMUNE REGULATION, 大学院・医歯学総合研究科, 教授 (60195013) ; MATASUDA HIROSHI TOKYO UNIVERSITY OF AGRICULTURE AND TECHNOLOGY, DEPARTMENT OF VETERINARY CLINIC, 大学院・共生科学技術研究部, 教授 (80145820) ; 設楽 浩志 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 研究員 (90321885)
• Project Period (FY): 2002 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥43,550,000 (Direct Cost: ¥33,500,000、Indirect Cost: ¥10,050,000); Fiscal Year 2004: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000); Fiscal Year 2003: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000); Fiscal Year 2002: ¥20,800,000 (Direct Cost: ¥16,000,000、Indirect Cost: ¥4,800,000)
• Keywords: transgenic mice / atopic dermatitis (eczema) / mast cells / T cells / Diphtheria toxin / Diphtheria toxin receptor / Tissue specific promotor / conditional cell depletion

Research Abstract

Atopic dermatitis (eczema : AD) is pruritic, chronic and relapsing inflammatory skin disease with predominantly childhood onset, but the symptoms can persist or begin in adulthood. It is also the most common cause of occupational skin disease in adults. Atopic dermatitis is associated with various immunological abnormalities and multiple environmental factors. Animal models are powerful tools to understand the bases and therapy of complex diseases. The NC/Nga inbred strain (NC), established from Japanese fancy mice in 1957, exhibits spontaneous severe dermatitis. The phenotypes of skin lesions in NC mice match the symptoms of the human atopic dermatitis, such as itching, erythema and hemorrhage with high titers of immunogloblin E (IgE) for various allergens. A similar skin inflammation has been observed in Stat6 deficient NC congenic mice with practically no IgE production. Genetic approaches indicate that numerous inherited factors can be responsible for the induction of skin inflammation. Genetically, the NC strain belongs to the Mus musculus domesticus group, which includes widely used laboratory strains, such as C57BL/6J.
Many attempts has been made to identify genes responsible for the AD-like skin lesions shown by NC mice, and only one major QTL locus named derm1 has been identified (Kohara et al. Immunogenetics, 1991). The locus identification is not so easy because any allergens for the spontaneous skin lesions of NC mice have not been identified so far and other QTLs than the major one showed little genetic effects for the disease. We tried to do an alternative method for identification of cellular and genetic bases of the diseases : the method is called TRECK (Toxin-Receptor Mediated Cell Knockout) method. The TRECK method has been developed by Kohno and his collaborators (Saito et al. Nature Biotech, 2001). We applied this method to deplete cells possibly responsible for the skin lesions of NC mice. The research is now still in progress.

Research Products

• [Journal Article] Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I α. ハ (2005)
  • Author(s): Sasaki, J., Sasaki, T., Yamazaki, M., Matsuoka, M., Taya, C., Shitara, H., Takasuga, S., Nishino, M., Mizuno, K., Wada, T., Miyazai, H., Watanabe, H., Iizuka, R., Kubo, S., Murata, S, Chiba, T., Maehama, T., Hamad, K., Kishimoto, H., Frohman, M.A., Tanaka, K., Penninger, J.M., Yonekawa, H., Suzuki, A., Kanaho, Y.
  • Journal Title: J. Exp. Med. 201 Pages: 859-870
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ovalbumin-specific IgE modulates ovalbumin-specific T-cell response after repetitive oral antigen administration (2005)
  • Author(s): Omata, N., 0hshima, Y., Yasutomi, M., Yamada, A., Karasuyama, H., Mayumi,M.
  • Journal Title: J. Allergy Clin. Immunol. 115 Pages: 822-827
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mycobacterium vaccae Reduces Scratching Behavior but not the Rash in NC Mice with Eczema : A Randomized, Blinded, Placebo-Controlled Trial (2005)
  • Author(s): Arkwright, P.D., Fujisawa, C., Tanaka, A., Matsuda H.
  • Journal Title: J. Invest. Dermatol. 124 Pages: 140-143
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Origins of mouse inbred strains deduced from whole-genome scanning by polymorphic microsatellite loci (2005)
  • Author(s): Sakai, T., KikKawa, Y., Miura, I., Inoue, I., Moriwaki, K., Shiroishi, T., Satta, Y., Takahata, N., Yonekawa, H
  • Journal Title: Mamm. Genome 16 Pages: 11-19
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type Iα. (2005)
  • Author(s): Sasaki, J., Sasaki, T., Yamazaki, M., Matsuoka, M., Taya, C., Shitara, H., Takasuga, S., Nishio, M., Mizuno, K., Wada, T., Miyazaki, H., Watanabe, H., Iizuka, R., Kubo, S., Murata, S., Chiba, T., Maehama, T., Hamada, K., Kishimoto, H., Frohman, M.A., Tanaka, K., Penninger, J.M., Yonekawa, H., Suzuki, A., Kanaho, Y.
  • Journal Title: J.Exp.Med. 201 Pages: 859-870
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Ovalbumin-specific IgE modulates ovalbumin-specific T-cell -response after repetitive oral antigen administration. (2005)
  • Author(s): Omata, N., Ohshima, Y, Yasutomi, M., Yamada, A., Karasuyama, H., Mayumi, M.
  • Journal Title: J.Allergy Clin.Immunol. 115 Pages: 822-827
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mycobacterium vaccae Reduces Scratching Behavior but not the Rash in NC Mice with Eczema : A Randomized, Blinded, Placebo-Controlled Trial. (2005)
  • Author(s): Arkwright, P.D., Fujisawa, C., Tanaka, A., Matsuda H.
  • Journal Title: J.Invest.Dermatol. 124 Pages: 140-143
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Origins of mouse inbred strains deduced from whole-genome scanning by polymorphic microsatellite loci. (2005)
  • Author(s): Sakai, T., Kikkawa, Y., Miura, I., Inoue, T., Moriwaki, K., Shiroishi, T., Satta, Y., Takahata, N., Yonekawa, H.
  • Journal Title: Mamm.Genome 16 Pages: 11-19
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I α (2005)
  • Author(s): Sasaki, J.et al.
  • Journal Title: J.Exp.Med. 201 Pages: 859-870
• [Journal Article] Origins of mouse inbred strains deduced from whole-genome scanning by polymorphic microsatellite loci. (2005)
  • Author(s): Sakai, T.et al.
  • Journal Title: Mamml.Genome 16 Pages: 11-19
• [Journal Article] Simple method of zygosity identification in transgenic mice by real-time quantitative PCR (2004)
  • Author(s): Sgitara, H.et al.
  • Journal Title: Transgenic Res. 13 Pages: 191-194
• [Journal Article] Liver Regeneration in Heparin-Binding EGF-like Growth Factor Transgenic Mice After Partial Hepatectomy. (2003)
  • Author(s): Kiso, S., Kawata, S., Tamura, S., Inui, Y., Yoshida, Y., Sawai, Y., Umeki, S., Ito, N., Yamada, A., Miyagawa, J., Higashiyama, S., Iwawaki, T., Saito, M., Taniguchi, N., Matsuzawa, Y., Kohno, K.
  • Journal Title: Gastmenteml 124 Pages: 701-707
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Long-term maintenance of IgE-mediated memory in mast cells in the absence of detectable serum IgE (2003)
  • Author(s): Kubo, S., Nakayama, T., Matsuoka, K., Yonekawa, H., Karasuyama, H
  • Journal Title: J. Immunol. 170 Pages: 775-780
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Liver Regeneration in Heparin-Binding EGF-like Growth Factor Transgenic Mice After Partial Hepatectomy. (2003)
  • Author(s): Kiso, S., Kawata, S., Tamara, S, Inui, Y, Yoshida, Y., Sawai, Y., Umeki, S., Ito, N., Yamada, A., Miyagawa, J., Higashiyama, S., Iwawaki, T., Saito, M., Taniguchi, N., Matsuzawa, Y., Kohno, K.
  • Journal Title: Gastroenterol. 124 Pages: 701-707
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Long-term maintenance of IgE-mediated memory in mast cells in the absence of detectable serum IgE. (2003)
  • Author(s): Kubo, S., Nakayama, T., Matsuoka, K., Yonekawa, H., Karasuyama, H.
  • Journal Title: J.Immunol. 170 Pages: 775-780
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] マウスラボマニュアル (第2版) (2003)
  • Author(s): 東京都臨床医学総合研究所・実験動物研究部門
  • Total Pages: 376
  • Publisher: シュプリンガーフェアラータ・束京
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Mouse Lab Manual (in Japanese) (2003)
  • Author(s): Yonekawa, H. et al. ed.
  • Total Pages: 376
  • Publisher: Springer Verlag Tokyo
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kubo S.et al.: "Long-term maintenance of IgE-mediated memory in mast cells in the absence of detectable serum IgE."J.Immunol.. 170. 775-780 (2003)
• [Publications] Sato, E. et al.: "Chronic inflammation in skin can be induced in IgE transgenic mice by a single challenge of multivalent antigen.."J.Allergy Clin.Immunol.. 111. 143-148 (2003)
• [Publications] 米川博通(著者兼編集代表): "マウスラボマニュアル(第2版)"シュプリンガーフェアラーク東京. 376 (2003)
• [Publications] Kubo S.et al.: "Long-term maintenance of IgE-mediated memory in mast cells in the absence of detectable serum IgE"J. Immunol.. (in press).
• [Publications] Hirahara K. et al.: "Chronic inflammation in skin can be induced in IgE transgenic mice by a single challenge of multivalent antigen"J. Allergy Clin. Immunol.. (in press).
• [Publications] 米川博通, 他: "マウスラボマニュアル(改訂版)"シュプリンガーフェアラーク東京(印刷中). 900