Establishment of better mouse models of Graves' disease and Grave's ophtahlmopathy

• Project/Area Number: 24790948
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Nagasaki University
• Principal Investigator: NAKAHARA Mami 長崎大学, 原爆後障害医療研究所, 客員研究員 (90622605)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 甲状腺自己免疫 / 甲状腺刺激ホルモン受容体 / 国際研究者交流：ドイツ / 国際情報交換、ドイツ

Research Abstract

(1) To determine the appropriate amounts of adenovirus, various amounts of adenovirus were used to immunize mice, revealing that the lower amounts of virus induced higher titers of TSAb and hyperthyroidism, the latter, however, did not last long. (2) Naturally occurring or immunization-induced Graves disease was not observed in mice generated by using SKG and ZAP-70 KO mice having various levels of defects in the signal transduction pathway in T lymphocytes. (3) Experiments of immunization of mice with TSHR + calsequestrin or collagen XIII plus exposure to cigarette smoke revealed that cigarette smoke exacerbated macrophage infiltration in the orbits.

Research Products

• [Journal Article] Disruption of transforming growth factor-・ signaling in thyroid follicular epithelial cells or intrathyroidal fibroblasts does not promote thyroid carcinogenesis (2014)
  • Author(s): Shimamura M, Nakahara M, Kurashige T, Yasui K, Nakashima M, Nagayama Y
  • Journal Title: Endocrine J Volume: 61(3) Pages: 297-302
  • Peer Reviewed
• [Journal Article] Disruption of transforming growth factor-beta signaling in thyroid follicular epithelial cells or intrathyroidal fibroblasts does not promote thyroid carcinogenesis. (2014)
  • Author(s): Shimamura M, Nakahara M, Kurashige T, Yasui K, Nakashima M, Nagayama Y.
  • Journal Title: Endocrine J Volume: 61 Pages: 297-302
  • Peer Reviewed
• [Journal Article] Postnatal Expression of BRAFV600E Does Not Induce Thyroid Cancer in Mouse Models of Thyroid Papillary Carcinoma. (2013)
  • Author(s): Shimamura M, Nakahara M, Orim F, Kurashige T, Mitsutake N, Nakashima M, Kondo S, Yamada M, Taguchi R, Kimura S, Nagayama Y
  • Journal Title: Endocrinology Volume: 154 Pages: 4423-30
  • DOI: 10.1210/en.2013-1174
  • NAID: 120005398105
  • Peer Reviewed
• [Journal Article] Prophylactic and therapeutic efficacies of a selective inhibitor of the immunoproteasome for Hashimoto's thyroiditis, but not for Graves' hyperthyroidism in mice (2012)
  • Author(s): Nagayama Y, Nakahara M, Shimamura M, Horie I, Arima K, Abiru N.
  • Journal Title: Clinical Experimental Immunology Volume: 168 Pages: 268-273
  • DOI: 10.1111/j.1365-2249.2012.04578.x
  • Peer Reviewed
• [Journal Article] Adoptive transfer of antithyrotropin receptor (TSHR) autoimmunity from TSHR knockout mice to athymic nude mice. (2012)
  • Author(s): Nakahara M, Johnson K, Eckstein A, Taguchi R, Yamada M, Abiru N, Nagayama Y.
  • Journal Title: Endocrinology Volume: 153 Pages: 2034-2042
  • DOI: 10.1210/en.2011-1846
  • NAID: 120004606860
  • Peer Reviewed
• [Journal Article] Minor contribution of cytotoxic T lymphocyte antigen 4 and programmed cell death 1 ligand 1 in immune tolerance against mouse thyrotropin receptor in mice
  • Author(s): Yasui J, Nakahara M, Shimamura M, Kurashige T, Kasui K, Abiru N, Kawakami A, Nagayama Y
  • Journal Title: Acta Med Nagasaki Volume: (in press)
  • NAID: 110009959607
  • Peer Reviewed
• [Remarks]
  • URL: http://www-sdc.med.nagasaki-u.ac.jp/index-sjis.html
• [Remarks] 長崎大学原爆後障害医療研究所
  • URL: http://www-sdc.med.nagasaki-u.ac.jp/index-sjis.html