Takashi Kuramoto1, Mayuko Yokoe2, Daisuke Tanaka2, Azusa Yuri2, Ai Nishitani2, Yuki Higuchi2, Kazuto Yoshimi2, Miyuu Tanaka3, Mitsuru Kuwamura4, Hiroshi Hiai5, Kenji Kabashima6, Tadao Serikawa7. 1. Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: tkuramot@anim.med.kyoto-u.ac.jp. 2. Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. 3. Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; Laboratory of Veterinary Pathology, Osaka Prefecture University, Izumisano, Osaka 598-8531, Japan. 4. Laboratory of Veterinary Pathology, Osaka Prefecture University, Izumisano, Osaka 598-8531, Japan. 5. Medical Innovation Center, Graduate School of Medicine, Kyoto University, Shogoin-kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan. 6. Department of Dermatology, Graduate School of Medicine, Kyoto University, Shogoin-kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan. 7. Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan; Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka 569-1094, Japan.
Abstract
BACKGROUND: Rats showing spontaneous atopic dermatitis (AD)-like skin lesions were observed in the Kyoto Fancy Rat Stock 4 (KFRS4) strain breeding colony. OBJECTIVE: To establish the KFRS4 rat as a model of AD. METHODS: The clinical symptoms of AD-like skin lesions were assessed by scoring the degree of dermatitis and examining scratching behavior. The transepidermal water loss was measured to evaluate skin barrier function. Cells infiltrating the skin lesions were identified using histological and immunohistological analyses. IgE and cytokine levels were measured to examine immune status. An ointment treatment experiment was carried out to characterize dermatitis in the KFRS4 rats. RESULTS: Dermatitis initially appeared around 4 months of age and rapidly worsened from 6 to 8 months of age. The skin lesions accompanied scratching behavior and were predominantly observed in females. The increased transepidermal water loss indicated skin barrier dysfunction. Extensive infiltration of eosinophils, mast cells and lymphocytes was observed in the skin lesions. The plasma IgE level increased in accord with increasing severity of dermatitis. The Th2 and Th17 cytokine mRNA levels were significantly higher in the skin-draining lymph nodes than those in the non-skin-draining lymph nodes. It was demonstrated that betamethasone improved the symptoms of dermatitis. These findings demonstrated that dermatitis in the KFRS4 rats closely resembled that seen in human AD. CONCLUSION: Female KFRS4 rats have the potential to serve as an animal model of human AD.
BACKGROUND:Rats showing spontaneous atopic dermatitis (AD)-like skin lesions were observed in the Kyoto Fancy Rat Stock 4 (KFRS4) strain breeding colony. OBJECTIVE: To establish the KFRS4 rat as a model of AD. METHODS: The clinical symptoms of AD-like skin lesions were assessed by scoring the degree of dermatitis and examining scratching behavior. The transepidermal water loss was measured to evaluate skin barrier function. Cells infiltrating the skin lesions were identified using histological and immunohistological analyses. IgE and cytokine levels were measured to examine immune status. An ointment treatment experiment was carried out to characterize dermatitis in the KFRS4 rats. RESULTS:Dermatitis initially appeared around 4 months of age and rapidly worsened from 6 to 8 months of age. The skin lesions accompanied scratching behavior and were predominantly observed in females. The increased transepidermal water loss indicated skin barrier dysfunction. Extensive infiltration of eosinophils, mast cells and lymphocytes was observed in the skin lesions. The plasma IgE level increased in accord with increasing severity of dermatitis. The Th2 and Th17 cytokine mRNA levels were significantly higher in the skin-draining lymph nodes than those in the non-skin-draining lymph nodes. It was demonstrated that betamethasone improved the symptoms of dermatitis. These findings demonstrated that dermatitis in the KFRS4 rats closely resembled that seen in humanAD. CONCLUSION: Female KFRS4 rats have the potential to serve as an animal model of humanAD.
Authors: Ju Ho Park; Ji Yeon Choi; Dong Ju Son; Eun Kyung Park; Min Jong Song; Mats Hellström; Jin Tae Hong Journal: Int J Mol Sci Date: 2017-03-30 Impact factor: 5.923