Analysis of filaggrin-null mice in dry environment to understand the pathogenic mechanism of atopic dermatitis

• Project/Area Number: 24791176
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Keio University
• Principal Investigator: KAWASAKI Hiroshi 慶應義塾大学, 医学部, 助教 (70445344)
• 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: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 皮膚炎症・再生学 / アトピー性皮膚炎 / 皮膚バリア / 乾燥環境 / フィラグリン

Research Abstract

Loss-of-function mutations in the filaggrin gene are major predisposing factors for atopic dermatitis. In this study, we hypothesized that dry environment might influence the impact of filaggrin deficiency and we evaluated filaggrin-null (Flg-/-) mice in dry condition. Dry condition exacerbated scaly skin gross phenotype in Flg-/- mice, which resembled Ichthyosis vulgaris, while skin in wild-type littermates were not apparently affected. Histological examination revealed acanthosis and large, thick scales focally in Flg-/- skin in dry condition, indicating abnormal cornification. Both of "inside-to-outside" and "outside-to-inside" permeation through Flg-/- stratum corneum were more enhanced in dry condition, as compared with wild-type stratum corneum. Thus, the skin phenotype and barrier disruption due to lack of filaggrin became more prominent in dry condition, indicating the importance of environmental factor in development of skin phenotype in filaggrin deficiency.

Research Products

• [Presentation] Exacerbation of the skin barrier function of filaggrin-null mice in dry environment (2013)
  • Author(s): Kawasaki H
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2013-12-13
• [Presentation] Filaggrin-null mice exhibit impaired stratum corneum barrier and enhanced percutaneous immune responses (2013)
  • Author(s): Kawasaki H
  • Organizer: the Asian Society for Pigment Cell Research and the Australasian Society for Dermatology Research conference 2013
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2013-05-19
• [Presentation] Exacerbation of the skin barrier function of filaggrin-null mice in dry environment.
  • Author(s): Kawasaki H, Kubo A, Hirano T, Amagai M
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] Filaggrin-null mice exhibit impaired stratum corneum barrier and enhanced percutaneous immune responses.
  • Author(s): Kawasaki H, Nagao K, Kubo A, Hata T, Mizuno H, Yamada T, Amagai M
  • Organizer: the Asian Society for Pigment Cell Research and the Australasian Society for Dermatology Research conference 2013
  • Place of Presentation: シドニー（オーストラリア）