title: Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT).
abstract: Childhood-onset dermatitis is one of the most common skin disorders in children. Although various mouse models that mirror aspects of dermatitis have become available, there is still a need for an animal model that develops dermatitis in childhood and is more suitable for performing tissue transplantation experiments. There is emerging evidence that peripheral blood T lymphocytes from patients with dermatitis have significantly increased telomerase activity. Here, we developed telomerase reverse transcriptase (TERT)-expressing transgenic (Tg) rats that spontaneously developed eczematous skin inflammation in childhood. Newborn TERT-Tg rats developed visible dermatitis in 56 % of cases, and the skin lesions microscopically showed spongiosis and acanthosis with infiltration of lymphocytes, eosinophils and mast cells. TERT-Tg rats with dermatitis exhibited increased CD4 (2.5-fold) and CD8 (fivefold) T cell numbers compared with dermatitis-free TERT-Tg rats. Stronger TERT activity was observed in the peripheral lymphocytes of dermatitis-positive TERT-Tg rats than those of dermatitis-free TERT-Tg rats. RT-PCR analysis revealed that IL-4 was markedly elevated in the spleen of dermatitis-positive TERT-Tg rats, and that interferon-gamma was increased in the dermatitis lesions. Moreover, skin grafting of TERT-Tg rats with dermatitis onto T cell-deficient nude rats demonstrated that the inflamed skin lesions could not be maintained. Taken together, the results suggest that TERT activation in T lymphocytes is one of the potential predisposing factors for dermatitis. Moreover, our results demonstrated that the TERT-Tg rats mirror aspects of human childhood-onset dermatitis and that these animals represent a potential animal model system for studying childhood-onset dermatitis.
authors.affiliation: Bioresource Center, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.|KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kaneko
authors.affiliation: Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, 329-0498, Japan.|Department of Dermatology, Jichi Medical University, Shimotsuke, Tochigi, 329-0498, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sato
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka, 565-0871, Japan.|Department of Food and Health Sciences, Fukuoka Women's University, Higashi-Ku, Fukuoka, 813-8529, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Hamada
authors.affiliation: KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka, 565-0871, Japan.|Japan Science and Technology Agency-Core Research for Evolutional Science and Technology, CREST, Osaka University, 1-3 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yagi
authors.affiliation: Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, 329-0498, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ohsawa
authors.affiliation: Department of Dermatology, Jichi Medical University, Shimotsuke, Tochigi, 329-0498, Japan.
authors.forename: Mamitaro
authors.initials: M
authors.lastname: Ohtsuki
authors.affiliation: Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, 329-0498, Japan.|Department of Organ Fabrication, Keio University School of Medicine, Shinjuku, Tokyo, 160-8582, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
authors.affiliation: Section of Mammalian Transgenesis, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Hirabayashi
authors.affiliation: Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, 329-0498, Japan. murakami@takasaki-u.ac.jp.|Laboratory of Tumor Biology, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, 60 Nakaorui, Takasaki, Gunma, 370-0033, Japan. murakami@takasaki-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
mesh_terms: D000818:Animals; D003872:Dermatitis / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D055647:Rats, Transgenic / Q000235:genetics*; D012867:Skin / Q000473:pathology; D013601:T-Lymphocytes / Q000502:physiology; D019098:Telomerase / Q000235:genetics*; D019076:Transgenes
chemical_list: D019098:Telomerase; C000625720:Tert protein, rat
keywords: Dermatitis; Telomerase reverse transcriptase (TERT); Transgenic rat