Molecular genetic analysis of atherosclerosis and atrial thrombosis rat model spontaneously induced by hypoactivity

• Project/Area Number: 25560368
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Applied health science
• Research Institution: The University of Tokushima
• Principal Investigator: IMOTO Issei 徳島大学, ヘルスバイオサイエンス研究部, 教授 (30258610)
• Co-Investigator(Renkei-kenkyūsha): TAJIMA Atsushi 徳島大学, 大学院・へルスバイオサイエンス研究部, 准教授 (10396864) ; NAKAYA Yutaka 徳島大学, 大学院・へルスバイオサイエンス研究部, 教授 (50136222) ; NIKAWA Takeshi 徳島大学, 大学院・へルスバイオサイエンス研究部, 教授 (20263824)
• Project Period (FY): 2013-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: スポーツ医学 / ゲノム / ラット / 遺伝学 / 高血圧 / 血栓 / エピジェネティックメモリー / 次世代シーケンサー

Research Abstract

We tried to identify genetic alterations responsible for atherosclerosis and atrial thrombosis with cerebral infarction spontaneously induced by hypoactivity in the SPORTS (Spontaneously Running Tokushima-Shikoku) rat model and molecular mechanisms of preventive effects of exercise on these phenotypes. We modified our self-made rat exon capture system and linkage analysis system, and identified a set of candidate responsible genes using these systems. Genome-wide expression analysis of vascular system also identified candidate genes associated with these phenotypes. In addition, we established systems to determine DNA methylation status and modify genome structure in rats. However, specific gene(s) and molecular mechanisms responsible for those phenotypes were unable to be determined even though using integrated analysis of omics data, suggesting that unknown genomic alterations and/or polygene-environment interactions contribute to acquire these phenotypes in this model.

Research Products

• [Journal Article] The expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer (2014)
  • Author(s): Kikuchi R, Kikuchi Y, Tsuda H, Maekawa H, Kozaki KI, Imoto I, Tamai S, Shiotani A, Iwaya K, Sakamoto M, Sekiya T, Matsubara O
  • Journal Title: Hum Cell
  • Peer Reviewed
• [Journal Article] Meta-analyses of blood homocysteine levels for gender and genetic association studies of the MTHFR C677T polymorphism in schizophrenia (2014)
  • Author(s): Nishi A, Numata S, Tajima A, Kinoshita M, Kikuchi K, Shimodera S, Tomotake M, Ohi K, Hashimoto R, Imoto I, Takeda M, Ohmori T
  • Journal Title: Schizophr Bullet
  • URL: http://schizophreniabulletin.oxfordjournals.org/content/early/2013/11/11/schbul.sbt154.long
  • Peer Reviewed
• [Journal Article] Novel PAX9 mutations cause nonsyndromic tooth agenesis in Japanese patients (2014)
  • Author(s): Mitsui SN, Y asue A, Masuda K, Watanabe K, Horiuchi S, Imoto I, T anaka E
  • Journal Title: J Dent Res Volume: 93(3) Issue: 3 Pages: 245-249
  • DOI: 10.1177/0022034513519801
  • Peer Reviewed
• [Journal Article] NF-κB Inducing Kinase, a Central Signaling Component of the Non-Canonical Pathway of NF-κB, Contributes to Ovarian Cancer Progression. (2014)
  • Author(s): Uno M, Saitoh Y, Mochida K, Tsuruyama E, Kiyono T, Imoto I, Inazawa J, Yuasa Y, Kubota T, Yamaoka S.
  • Journal Title: PLoS One Volume: 9(2) Issue: 2 Pages: e88347-e88347
  • DOI: 10.1371/journal.pone.0088347
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Specific molecular signatures of non-tumor liver tissues may predict a risk for development of hepatocellular carcinoma (2014)
  • Author(s): Utsunomiya T, Shimada M, Morine Y, Tajima A, Imoto I
  • Journal Title: Cancer Sci Volume: 印刷中 Issue: 7 Pages: 749-754
  • DOI: 10.1111/cas.12431
  • Peer Reviewed
• [Journal Article] The expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer. (2014)
  • Author(s): Kikuchi R, Kikuchi Y, Tsuda H, Maekawa H, Kozaki KI, Imoto I, Tamai S, Shiotani A, Iwaya K, Sakamoto M, Sekiya T, Matsubara O.
  • Journal Title: Hum Cell Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Meta-analyses of blood homocysteine levels for gender and genetic association studies of the MTHFR C677T polymorphism in schizophrenia. (2014)
  • Author(s): Nishi A, Numata S, Tajima A, Kinoshita M, Kikuchi K, Shimodera S, Tomotake M, Ohi K, Hashimoto R, Imoto I, Takeda M, Ohmori T.
  • Journal Title: Schizophr Bull Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Integrated genomic and functional analyses reveal glyoxalase I as a novel metabolic oncogene in human gastric cancer. (2014)
  • Author(s): Hosoda F, Inazawa J, et al.
  • Journal Title: Oncogene. Volume: in press Issue: 9 Pages: 1196-206
  • DOI: 10.1038/onc.2014.57
  • Peer Reviewed
• [Journal Article] Early results of omitting completion axillary lymph node dissection in sentinel lymph node metastasis-positive breast cancer patients (2013)
  • Author(s): Honda J, Matsuoka H, Hirose C, Nagao T, Y oshida T, T akahashi M, Imoto I, Sasa S
  • Journal Title: Advances Breast Cancer Res Volume: 2 Issue: 04 Pages: 126-132
  • DOI: 10.4236/abcr.2013.24021
  • Peer Reviewed
• [Journal Article] Impact of annual BMI gain on obesity development in Japanese 6-year-old nonobese children (2013)
  • Author(s): Kori H, Sei M, Nakahori Y, Imoto I
  • Journal Title: Pediatr Int Volume: 55(6) Issue: 6 Pages: 761-766
  • DOI: 10.1111/ped.12172
  • Peer Reviewed
• [Journal Article] NF90 in posttranscriptional gene regulation and microRNA biogenesis. (2013)
  • Author(s): Masuda K, Kuwano Y, Nishida K, Rokutan K, Imoto I.
  • Journal Title: Int J Mol Sci. Volume: 14(8) Issue: 8 Pages: 17111-21
  • DOI: 10.3390/ijms140817111
  • Peer Reviewed
• [Journal Article] Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia. Epigenetics (2013)
  • Author(s): Kinoshita M, Numata S, Tajima A, Shimodera S, Imoto I, Ohmori T
  • Journal Title: Epigenetics Volume: 8(6) Issue: 6 Pages: 584-590
  • DOI: 10.4161/epi.24621
  • Peer Reviewed
• [Journal Article] Replication study and meta-analysis of non-obstructive azoospermia in Japanese populations (2013)
  • Author(s): Sato Y, Jinam T, Iwamoto T, Yamauchi T, Yamauchi A, Imoto I, Inoue I, Tajima A
  • Journal Title: Biol Reprod Volume: 88(4) Pages: 87-87
  • Peer Reviewed
• [Journal Article] Replication study and meta-analysis of human nonobstructive azoospermia in Japanese populations. (2013)
  • Author(s): Sato Y
  • Journal Title: Biol Reprod Volume: 88 Issue: 4 Pages: 87-87
  • DOI: 10.1095/biolreprod.112.106377
  • Peer Reviewed
• [Presentation] 次世代シークエンサー解析により診断したSENDA小児例 (2013)
  • Author(s): 岡本伸彦, 他
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 江陽グランドホテル(宮城県仙台市)
  • Year and Date: 2013-11-22
• [Presentation] ゲノムワイドな異常DNAメチル化探索による新規メチル化標的喫煙関連肺腺癌抑制遺伝子の同定 (2013)
  • Author(s): 梶浦耕一郎, 他
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県横浜市)
  • Year and Date: 2013-10-03
• [Presentation] ゲノムワイドな異常DNAメチル化探索による新規メチル化標的喫煙関連肺腺癌抑制遺伝子の同定 (2013)
  • Author(s): 梶浦 耕一郎, 井本逸勢、増田清士、田嶋敦、近藤和也、丹黒章
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)横浜市
• [Presentation] 次世代シークエンサー解析により診断したSENDA 小児例 (2013)
  • Author(s): 岡本伸彦、長谷川龍志、池田妙、山崎藍、井本逸勢
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 江陽グランドホテル（宮城県仙台市）
• [Remarks] 徳島大学・大学院へルスバイオサイエンス研究部・人類遺伝学
  • URL: http://www.tokushima-u.ac.jp/med/culture/jinruiiden/
• [Remarks] 徳島大学医学部人類遺伝学分野
  • URL: http://www.tokushima-u.ac.jp/med/culture/jinruiiden/