乾癬モデルの紹介

乾癬は表皮角質細胞増殖の特徴的な皮膚病で、先天性免疫及び適応性免疫システムの細胞及び分子が介在し、遺伝やエピジェネティクス、環境要素によって総合的に作用した結果です。よく使われる動物乾癬モデルはイミキモド(imiquimod)誘導の皮膚損傷及び皮膚炎モデルで、その表現型はヒトの乾癬に似しています。

乾癬マウスモデルで、標準スコアリングシステムでイミキモドによる膚損傷状態、マウスの皮疹及び脱皮の症状をモニタリングして、皮膚表皮が肥厚している様子が観察されます。組織病理学解析では主に角質化不全及び真皮に炎症性白血球湿潤する見られます。IL-23/IL-17の炎症促進作用は最も重要な乾癬発病のメカニズムだといわれます。。イミキモド誘導乾癬モデルでは、IL-17サイトカインレベルは上昇します。

バイオサイトジェンはB-hIL17Aマウス(ヒトIL-17A遺伝子をマウスIL-17A遺伝子に置き換える)を用いて、IMQの誘導で乾癬マウスモデルを構築し、乾癬薬物の前臨床研究のために有効なツールを提供し、ヒトIL-17Aターゲットの薬物療法の研究の為に便利を提供しています。

Generation of B-hIL17A Mice and its phenotypic analysis

Basic Information

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Protein Expression Analysis

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Serum from wild type (WT) C57BL/6 and homozygous B-hIL17A mice were analyzed by ELISA.

Mouse IL17A was detectable in the WT mice, while human IL17A was detectable in the homozygous B-hIL17A mice.



Schematic diagram-Spleen

Analysis of leukocytes cell subpopulation in B-hIL17A mice

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Analysis of leukocytes subpopulation in spleen.Splenocytes were isolated from C57BL/6 and B-hIL17A mice (n=3) and profiled by flow cytometry. As shown in the panels above, leukocytes subpopulations in homozygous B-hIL17A mice are similar to those in the C57BL/6 mice, indicating that development of T, NK, Monocyte, DC and macrophage cells are not affected by the knock-in of hIL17A.

 

Analysis of T cell subpopulation in B-hIL17A mice

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Analysis of T cell subpopulation in spleen.Lymphocytes were isolated from spleen in C57BL/6 and B-hIL17A mice (n=3). T cells subpopulations were profiled by flow cytometry. As shown above, the T cell subpopulations in homozygous B-hIL17A mice are similar to those in the C57BL/6 mice, indicating that T cell development is not affected by the introduction of hIL17A.

 

IMQ-誘導乾癬モデルの構築及びその表現型解析

IMQ-誘導乾癬モデル


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IMQ cream was applied topically on left ear and back, QD x 8.


C57BL/6マウス乾癬モデルの耳の厚さ及び臨床スコアリング

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Mice (n=5) were scored daily for up to 8 days for clinical signs of skin inflammation following treatment with either control vaseline or IMQ cream (A-D). Results showed that IMQ significantly increased clinical signs of skin inflammation. Ear thickness was also increased by IMQ treatment (E).


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 IMQ increased thickness of sections of ear and back skin of mice treated with IMQ cream (H&E). B. IMQ increased skin thickness measurement. Five random points were selected and measured. The results showed that IMQ significantly increased epidermal thickness in ear and back skin. Scale bar: 100 um.


B-hIL17Aマウス乾癬モデルの耳の厚さ及び臨床スコアリング


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Mice (n=5) were scored daily for up to 8 days for clinical signs of skin inflammation following treatment with either control vaseline or IMQ cream (A-D). Results showed that IMQ significantly increased clinical signs of skin inflammation. Ear thickness was also increased by IMQ treatment (E).

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IMQ increased thickness of sections of ear and back skin of mice treated with IMQ cream (H&E). B. IMQ increased skin thickness measurement. Five random points were selected and measured. The results showed that IMQ significantly increased epidermal thickness in ear and back skin. Scale bar: 100 um.


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