Generation of mosaic model of epidermolysis bullosa by inactivation of X chromosome.

• Project/Area Number: 26670516
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Hokkaido University
• Principal Investigator: NISHIE Wataru 北海道大学, 大学病院, 講師 (20443955)
• Co-Investigator(Kenkyū-buntansha): NATSUGA Ken 北海道大学, 大学病院, 助教 (70645457)
• Project Period (FY): 2014-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 皮膚病態学 / 皮膚病理学

Outline of Final Research Achievements

The popups of this study is to generate a mosaic model of epidermolysis bullosa by inactivation of X chromosome. We have generated transgenic (Tg) mice with tetracycline response plasmid expressing human type XVII collagen (COL17) cDNA, and then crossed with the Tg mice expressing reverse tetracycline transactivator driven under keratin 14 promoter on X-chromosome. When primary keratinocytes from the double Tg mice were treated with doxycycline in culture, increased human COL17 gene expression was observed; however, COL17 protein expression was not induced. These results indicate that it may be challenging for this method to obtain mice with high inducible level of COL17, which is needed to be improved.

Research Products

• [Journal Article] Context-Dependent Regulation of Collagen XVII Ectodomain Shedding in Skin. (2015)
  • Author(s): Nishie W, Natsuga K, Iwata H, Izumi K, Ujiie H, Toyonaga E, Hata H, Nakamura H, Shimizu H.
  • Journal Title: Am J Pathol Volume: in press Issue: 5 Pages: 1361-71
  • DOI: 10.1016/j.ajpath.2015.01.012
  • NAID: 120005752843
  • Peer Reviewed / Open Access
• [Journal Article] In vivo analysis of IgE autoantibodies in bullous pemphigoid: A study of 100 cases. (2015)
  • Author(s): Moriuchi R, Nishie W, Ujiie H, Natsuga K, Shimizu H.
  • Journal Title: J Dermatol Sci Volume: 78 Issue: 1 Pages: 21-25
  • DOI: 10.1016/j.jdermsci.2015.01.013
  • Peer Reviewed
• [Presentation] One amino acid deletion in type XII collagen-binding domain of plectin with a truncation mutation underlies epidermolysis bullosa simplex. (2014)
  • Author(s): Natsuga K, Nishie W, Nishimura M, Nakamura H, Shimizu H.
  • Organizer: The 39th Annual Meeting of the Japanese Society of Invesitigative Dermatology
  • Place of Presentation: ホテル阪急エキスポパーク（吹田市）
  • Year and Date: 2014-12-12 – 2014-12-14