Generation of salivary gland-specific injury model mouse and elucidation of repair mechanism by EGFR2 / MUC1 pathway

• Project/Area Number: 17K11633
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Tsurumi University
• Principal Investigator: MATSUMOTO Naoyuki 鶴見大学, 歯学部, 准教授 (20386080)
• Co-Investigator(Kenkyū-buntansha): 梁 洪淵 鶴見大学, 歯学部, 講師 (10298268) ; 内田 仁司 鶴見大学, 歯学部, 学内講師 (20736996) ; 井上 裕子 日本薬科大学, 薬学部, 教授 (50367306) ; 中山 亮子 鶴見大学, 歯学部, 助教 (50749843) ; 斎藤 一郎 鶴見大学, 歯学部, 教授 (60147634)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 唾液腺 / 組織傷害 / 遺伝子改変マウス / 遺伝子改変動物 / 唾液腺傷害 / EGFR2 / MUC-1 / apoptosis / 口腔病理学

Outline of Final Research Achievements

It is difficult to accurately evaluate the effect of regenerative therapy in conventional mouse models of salivary gland injury, because various organs other than salivary glands are injured. Therefore, an animal model of salivary gland injury has been required.
In this study, we established a salivary gland-specific injury model mouse by gene modification using the Toxin receptor-mediated cell knockout (TRECK) as a model of salivary gland injury. Diphtheria toxin (DT) was injected into the transgenic mouse, and the amount of pilocarpine-stimulated salivary secretion was measured. As a result, it decreased to about 55% 168 hours after the administration of DT. Furthermore, histological examination revealed an increase of TUNEL-positive apoptotic cell as compared with the wild type.

Academic Significance and Societal Importance of the Research Achievements

本研究では唾液腺局所に発現するプロモーターによる遺伝子改変マウスを作出し、唾液腺特異的に組織が障害されることを確認した。この遺伝子改変マウスはこれまでにない病態モデルとなり、唾液腺障害に起因する唾液分泌障害のメカニズムの解析や、唾液腺組織再生治療の開発の為に、唾液腺を特異的に障害するモデル動物の開発が極めて有効な研究戦略となると考えられる。
今後、この遺伝子改変マウスを利用して組織傷害や再生の詳細を検討する。

Research Products

• [Journal Article] What Are the Major Causes of Dry Mouth in Elderly Adults? (2020)
  • Author(s): Matsumoto Naoyuki、Ushikoshi-Nakayama Ryoko、Yamazaki Tomoe、Kaneko Mie、Saito Ichiro
  • Journal Title: Current Oral Health Reports Volume: - Issue: 2 Pages: 165-167
  • DOI: 10.1007/s40496-020-00262-6
  • Peer Reviewed
• [Journal Article] Pulmonary activation of vitamin D₃ and preventive effect against interstitial pneumonia (2019)
  • Author(s): Tsujino Ichiro、Ushikoshi-Nakayama Ryoko、Yamazaki Tomoe、Matsumoto Naoyuki、Saito Ichiro
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 65 Issue: 3 Pages: 245-251
  • DOI: 10.3164/jcbn.19-48
  • NAID: 130007740756
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Effect of gummy candy containing ubiquinol on secretion of saliva: A randomized, double-blind, placebo-controlled parallel-group comparative study and an in vitro study (2019)
  • Author(s): Ushikoshi-Nakayama Ryoko、Ryo Koufuchi、Yamazaki Tomoe、Kaneko Mie、Sugano Tomoko、Ito Yumi、Matsumoto Naoyuki、Saito Ichiro
  • Journal Title: PLOS ONE Volume: 14 Issue: 4 Pages: e0214495-e0214495
  • DOI: 10.1371/journal.pone.0214495
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of the effect of a heat-killed lactic acid bacterium, Enterococcus faecalis 2001, on oral candidiasis (2019)
  • Author(s): Yamazaki T.、Ushikoshi-Nakayama R.、Shirone K.、Suzuki M.、Abe S.、Matsumoto N.、Inoue H.、Saito I.
  • Journal Title: Beneficial Microbes Volume: 10 Issue: 6 Pages: 661-669
  • DOI: 10.3920/bm2018.0115
  • Peer Reviewed
• [Remarks] 鶴見大学歯学部 病理学講座
  • URL: http://ccs.tsurumi-u.ac.jp/dental/kouza/byouri/originalpaper.html