Induction of aoutoantibodies to BP230 and analysis of new function of BP230 using gene-engineered mouse

• Project/Area Number: 26293254
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Hirosaki University
• Principal Investigator: SAWAMURA Daisuke 弘前大学, 医学研究科, 教授 (60196334)
• Co-Investigator(Kenkyū-buntansha): 松崎 康司 弘前大学, 医学部附属病院, 講師 (50322946) ; 中野 創 弘前大学, 医学研究科, 准教授 (90281922)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
• Keywords: 遺伝子 / 自己免疫 / 皮膚 / 水疱 / マウス

Outline of Final Research Achievements

Bullous pemphigoid is a skin disease which shows generalized blisters and occurs mostly in the elderly. This disease is characterized by autoantibodies to basement membrane zone and considered as autoimmune blistering disease. In this study, we generated knockout mouse of BP230 and also conditional knockout mouse without epidermal BP230 expression. The results demonstrated that BP230 plays an important role in muscle function. Furthermore, BP230 has great contributions to stability of biding between the epidermis and the dermis.

Research Products

• [Journal Article] Multiple milia as an isolated skin manifestation of dominant dystrophic epidermolysis bullosa: Evidence of phenotypic variability. (2017)
  • Author(s): Akasaka E, Nakano H, Takagi Y, Toyomaki Y, Sawamura D
  • Journal Title: Pediatr Dermatol Volume: 34 Issue: 2
  • DOI: 10.1111/pde.13047
  • Peer Reviewed / Open Access
• [Journal Article] The 6-year follow-up of a Japanese patient with silent erythropoietic protoporphyria. (2017)
  • Author(s): Mizawa M, Makino T, Furukawa F, Torai R, Nakano H, Sawamura D, Shimizu T.
  • Journal Title: JAAD Case Rep. Volume: 3 Issue: 3 Pages: 169-171
  • DOI: 10.1016/j.jdcr.2017.01.025
  • Peer Reviewed / Open Access
• [Journal Article] An <i>ATP2A2</i> Missense Mutation in a Japanese Family with Darier Disease: A Case Report and Review of the Japanese Darier Disease Patients with <i>ATP2A2</i> Mutations (2017)
  • Author(s): Li M, Higashi N, Nakano H, Saeki H.
  • Journal Title: Journal of Nippon Medical School Volume: 84 Issue: 5 Pages: 246-250
  • DOI: 10.1272/jnms.84.246
  • NAID: 130006206426
  • ISSN: 1345-4676, 1347-3409
  • Peer Reviewed / Open Access
• [Journal Article] C-Terminal Processing of Collagen XVII Induces Neoepitopes for Linear IgA Dermatosis Autoantibodies (2017)
  • Author(s): Toyonaga Ellen、Nishie Wataru、Izumi Kentaro、Natsuga Ken、Ujiie Hideyuki、Iwata Hiroaki、Yamagami Jun、Hirako Yoshiaki、Sawamura Daisuke、Fujimoto Wataru、Shimizu Hiroshi
  • Journal Title: Journal of Investigative Dermatology Volume: 137 Issue: 12 Pages: 2552-2559
  • DOI: 10.1016/j.jid.2017.07.831
  • NAID: 120006540048
  • Peer Reviewed / Open Access
• [Journal Article] Prevalence of skin infections caused by Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus ?in?Japan, particularly in Ishigaki, Okinawa (2017)
  • Author(s): Takadama S, Nakaminami H, Aoki S, Akashi M, Wajima T, Ikeda M, Mochida A, Shimoe F, Kimura K, Matsuzaki Y, Sawamura D, Inaba Y, Oishi T, Nemoto O, Baba N, Noguchi N
  • Journal Title: J Infect Chemother. Volume: 23 Issue: 11 Pages: 800-803
  • DOI: 10.1016/j.jiac.2017.04.016
  • Peer Reviewed / Open Access
• [Journal Article] Multiple familial trichoepithelioma with a novel mutation of the CYLD gene. (2017)
  • Author(s): Fujii A, Matsuyama K, Mizutani Y, Kanoh H, Nakano H, Seishima M.
  • Journal Title: J Dermatol Volume: 44 Issue: 9
  • DOI: 10.1111/1346-8138.13901
  • Peer Reviewed / Open Access
• [Journal Article] Modulation of Stimulator of Interferon Genes (STING) Expression by Interferon-γ in Human Keratinocytes (2017)
  • Author(s): Nishikawa Y, Matsuzaki Y, Kimura K, Rokunohe A, Nakano H, Sawamura D
  • Journal Title: Biochemical Genetics Volume: 56 Issue: 1-2 Pages: 93-102
  • DOI: 10.1007/s10528-017-9832-7
  • Peer Reviewed / Open Access
• [Journal Article] Case of late-onset erythropoietic protoporphyria with myelodysplastic syndrome who has homozygous IVS3-48C polymorphism in the ferrochelatase gene. (2016)
  • Author(s): Suzuki H, Kikuchi K, Fukuhara N, Nakano H, Aiba S.
  • Journal Title: J Dermatol Volume: - Issue: 6 Pages: 651-655
  • DOI: 10.1111/1346-8138.13709
  • Peer Reviewed / Open Access
• [Journal Article] Elevated levels of circulating immunoglobulin E autoantibodies against BP180 and BP230 in an intractable case of bullous pemphigoid. (2016)
  • Author(s): Akasaka E, Hagiwara C, Takiyoshi N, Aizu T, Nakano H, Sawamura D, Ota T
  • Journal Title: J Dermatol Sci. Volume: 84 Issue: 1 Pages: 110-113
  • DOI: 10.1016/j.jdermsci.2016.07.011
  • Peer Reviewed / Open Access
• [Journal Article] Extracellular cleavage of collagen XVII is essential for correct cutaneous basement membrane formation. (2016)
  • Author(s): Nishimura M, Nishie W, Shirafuji Y, Shinkuma S, Natsuga K, Nakamura H, Sawamura D, Iwatsuki K, Shimizu H
  • Journal Title: Hum Mol Genet Volume: 15;25(2) Issue: 2 Pages: 328-39
  • DOI: 10.1093/hmg/ddv478
  • NAID: 120005868259
  • Peer Reviewed / Open Access
• [Journal Article] Diaminodiphenyl Sulfone-Induced Hemolytic Anemia and Alopecia in a Case of Linear IgA Bullous Dermatosis. (2015)
  • Author(s): Akasaka E, Kayo SJ, Nakano H, Ishii N, Hashimoto T, Sawamura D.
  • Journal Title: Case Reports in Dermatology Volume: 7 Issue: 2 Pages: 183-6
  • DOI: 10.1159/000438506
  • Peer Reviewed / Open Access
• [Journal Article] Mycosis fungoides bullosa associated with bullous pemphigoid. (2015)
  • Author(s): Korekawa A, Kaneko T, Nakajima K, Rokunohe D, Akasaka E, Nakano H, Sawamura D, Fukui T, Takiyoshi N, Kitamura H, Harada K
  • Journal Title: Int J Dermatol Volume: 54 Issue: 9
  • DOI: 10.1111/ijd.12821
  • Peer Reviewed / Open Access
• [Journal Article] Oral lichen planus with antibodies to desmogleins 1 and 3. (2015)
  • Author(s): Kinjyo C, Kaneko T, Korekawa A, Rokunohe A, Aizu T, Matsuzaki Y, Nakano H, Sawamura D.
  • Journal Title: J Dermatol Volume: 42 Issue: 1 Pages: 40-41
  • DOI: 10.1111/1346-8138.12661
  • Peer Reviewed / Open Access
• [Journal Article] Anti-laminin γ1 pemphigoid associated with ulcerative colitis and psoriasis vulgaris showing autoantibodies to laminin γ1, type XVII collagen and laminin-332. (2015)
  • Author(s): Akasaka E, Nakano H, Korekawa A, Fukui T, Kaneko T, Koga H, Hashimoto T, Sawamura D.
  • Journal Title: Eur J Dermatol Volume: 26 Issue: 2 Pages: 198-199
  • DOI: 10.1684/ejd.2014.2499
  • Peer Reviewed / Open Access
• [Journal Article] Two Japanese familial cases of punctate palmoplantar keratoderma caused by a novel AAGAB mutation, c.191_194delCAAA. (2015)
  • Author(s): Akasaka E, Okawa Y, Nakano H, Takiyoshi N, Rokunohe D, Toyomaki Y, Sawamura D, Sueki H.
  • Journal Title: J Dermatol Sci Volume: 78 Issue: 2 Pages: 156-158
  • DOI: 10.1016/j.jdermsci.2015.02.004
  • Peer Reviewed / Open Access
• [Journal Article] Severe scoliosis associated with the WNT10A mutation. (2015)
  • Author(s): Koguchi-Yoshioka H, Wataya-Kaneda M, Nakano H, Tanemura A, Akasaka E, Sawamura D, Katayama I.
  • Journal Title: J Dermatol Volume: 42 Issue: 3 Pages: 322-323
  • DOI: 10.1111/1346-8138.12762
  • Peer Reviewed / Open Access
• [Journal Article] A palindromic motif in the -2084 to -2078 upstream region is essential for ABCA12 promoter function in cultured human keratinocytes (2014)
  • Author(s): Shimizu Y, Ogawa Y, Sugiura K, Takeda J, Sakai-Sawada K, Yanagi T, Kon A, Sawamura D, Shimizu H, Akiyama M
  • Journal Title: Sci Rep Volume: 4 Issue: 1 Pages: 6737-6737
  • DOI: 10.1038/srep06737
  • Peer Reviewed / Open Access
• [Journal Article] Atopic diathesis in hypohidrotic/anhidrotic ectodermal dysplasi (2014)
  • Author(s): Hanako Koguchi-Yoshioka1, Mari Wataya-Kaneda1#, Mizuki Yutani1, Hiroyuki Murota1, Hajime Nakano2, Daisuke Sawamura2, Ichiro Katayam
  • Journal Title: Acta Derm Venereol. Volume: ? Issue: 4 Pages: 476-479
  • DOI: 10.2340/00015555-1978
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 最近経験した遺伝性皮膚疾患 (2017)
  • Author(s): 澤村大輔
  • Organizer: 第133回山陰・第29回島根合同開催地方会
  • Invited
• [Presentation] 遺伝性皮膚疾患の遺伝子診断 (2017)
  • Author(s): 中野 創
  • Organizer: 函館皮膚科医会学術講演
  • Invited
• [Presentation] 皮膚科新薬の効果と最近経験した興味深い症例 (2017)
  • Author(s): 松﨑康司
  • Organizer: 第124回弘前皮膚科専門医会
  • Invited
• [Presentation] 栄養状態と皮膚の健康―創傷治癒から帯状疱疹までー (2017)
  • Author(s): 中野 創
  • Organizer: 第32回東北静脈経腸栄養研究会
  • Invited
• [Presentation] 外科手術を契機に再燃し免疫グロブリン大量静注時に血小板減少をきたした水疱性類天疱瘡 (2017)
  • Author(s): 赤坂英二郎、高橋実か、原 憲司、是川あゆ美、会津隆幸、中野 創、澤村大輔
  • Organizer: 第39回水疱症研究会
• [Presentation] ヒドロキシクロロキンによる急性汎発性発疹性膿疱症（AGEP） (2017)
  • Author(s): 金子高英、古川和仁、萩原千尋、滝吉典子、中野 創、澤村大輔、桜庭裕丈
  • Organizer: 第81回日本皮膚科学会東京支部学術大会
• [Presentation] 遺伝性皮膚疾患のトピックス (2016)
  • Author(s): 澤村大輔
  • Organizer: 皮膚科セミナー
  • Place of Presentation: 前橋商工会議所（群馬県・前橋市）
  • Year and Date: 2016-12-15
  • Invited
• [Presentation] 栄養障害型表皮水疱症の遺伝子診断における末梢血単核球のⅦ型コラーゲン発現についての検討 (2016)
  • Author(s): 赤坂英二郎、中野 創、神田由起、鷹木由里子、豊巻由香、澤村大輔
  • Organizer: 第38回水疱症研究会
  • Place of Presentation: ラフレさいたま（埼玉県・さいたま市）
  • Year and Date: 2016-11-29
• [Presentation] 表皮水疱症の最近の話題 (2016)
  • Author(s): 澤村大輔
  • Organizer: 皮膚病態学アフェレシスフォーラム
  • Place of Presentation: ホテルグランヴィア大阪（大阪府・大阪市）
  • Year and Date: 2016-08-04
  • Invited
• [Presentation] 日常診療でみられる遺伝性皮膚疾患、遺伝子診断 (2016)
  • Author(s): 澤村大輔
  • Organizer: 第６回城南皮膚病カンファレンス
  • Place of Presentation: 渋谷エクセルホテル東急（東京都・渋谷区）
  • Year and Date: 2016-07-28
  • Invited
• [Presentation] 稗粒腫を初発症状とし家系内で異なる臨床病型を呈した優性栄養障害型表皮水疱症の1家系例 (2016)
  • Author(s): 赤坂英二郎、中野 創、鷹木由里子、豊巻由香、澤村大輔
  • Organizer: 第115回日本皮膚科学会総会
  • Place of Presentation: 国立京都国際会館(京都府・京都市）
  • Year and Date: 2016-06-03
• [Presentation] 栄養障害型表皮水疱症における末梢血単核球から分離したmRNAを用いたCOL7A1変異検索 (2016)
  • Author(s): 赤坂英二郎、中野 創、神田由紀、鷹木由里子、豊巻由香、澤村大輔
  • Organizer: 第23回分子皮膚科学フォーラム
  • Place of Presentation: ホテルグランヴィア大阪（大阪府・大阪市）
  • Year and Date: 2016-04-15
• [Presentation] Mutational analysis of dystrophic epidermolysis bullosa. (2016)
  • Author(s): Akasaka E, Nakano H, Sawamura D
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: 国立京都国際会館（京都府・京都市）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] 表皮水疱症の最近の話題 (2015)
  • Author(s): 澤村大輔
  • Organizer: 第4回東京水疱症研究会
  • Place of Presentation: フォーシーズンズ丸ノ内（東京都千代田区）
  • Year and Date: 2015-12-03
  • Invited
• [Presentation] 表皮水疱症の診断基準と最新の治療研究報告 (2015)
  • Author(s): 澤村大輔
  • Organizer: 仙台市医療講演・相談会難病医療法から学ぶ表皮水疱症(EB) Q&A
  • Place of Presentation: 日立システムズホール仙台（宮城県仙台市）
  • Year and Date: 2015-11-28
  • Invited
• [Presentation] 著名な好酸球増多と浮腫性紅斑を示し血漿交換が奏功した水疱性類天疱瘡 (2015)
  • Author(s): 赤坂英二郎
  • Organizer: 第37回水疱症研究会
  • Place of Presentation: コラッセ福島（福島県福島市）
  • Year and Date: 2015-09-26
• [Presentation] 優性栄養障害型表皮水疱症の遺伝カウンセリング～G2251E変異について～ (2015)
  • Author(s): 赤坂英二郎
  • Organizer: 第39回日本遺伝カウンセリング学会学術集会
  • Place of Presentation: 三井ガーデンホテル千葉（千葉県千葉市）
  • Year and Date: 2015-06-26
• [Presentation] 表皮水疱症：その臨床と最近の治療 (2015)
  • Author(s): 澤村大輔
  • Organizer: 第３回北海道皮膚IVIG療法研究会
  • Place of Presentation: 札幌プリンスホテル国際館パミール（札幌）
  • Year and Date: 2015-02-06
  • Invited
• [Presentation] 表皮下水疱症の臨床と治療 (2014)
  • Author(s): 澤村大輔
  • Organizer: 第1回福島皮膚科水疱症フォーラム
  • Place of Presentation: 福島ビューホテル（福島）
  • Year and Date: 2014-11-07
  • Invited
• [Presentation] 複数の神経ブロックを併用して腋窩郭清を施行した重症型表皮水疱症の１例． (2014)
  • Author(s): 金子高英、会津隆幸、松井彰伸、滝吉典子、六戸大樹、松﨑康司、中野 創、澤村大輔、北山眞任、橋本 浩、廣田和美
  • Organizer: 第29回日本皮膚外科学会総会・学術集会
  • Place of Presentation: 和歌山マリーナシティ ロイヤルパインズホテル（和歌山）
  • Year and Date: 2014-09-13 – 2014-09-14
• [Presentation] 栄養障害型表皮水疱症133家系のCOL7A1遺伝子変異解析 (2014)
  • Author(s): 2.赤坂英二郎、中野 創、鷹木由里子、豊巻由香、中野あおい、玉井克人、野村和夫、三橋善比古、橋本 功、澤村大輔
  • Organizer: 第113回日本皮膚科学会総会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-05-30 – 2014-06-01
• [Book] 皮膚科研修ノート (2016)
  • Author(s): 澤村大輔、中野 創、宮地良樹、戸倉新樹、山本俊幸、山崎研志、佐山浩二、池田政身、多田譲治、盛山吉弘、伊藤周作、井上雄二、木花いずみ、江川清文、浅田秀夫、日野治子、渡辺大輔、清水 晶、川口博史、望月 隆
  • Total Pages: 712
  • Publisher: 診断と治療社