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Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT)

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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.

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Abbreviations

AD:

Atopic dermatitis

Tg:

Transgenic

TERT:

Telomerase reverse transcriptase

IL:

Interleukin

IFN:

Interferon

SPF:

Specific pathogen-free

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Acknowledgments

We would like to thank Drs. M. Kubo and T. Banno for discussions, Ms. M. Kato, A. Ishikawa, and A. Takata for technical assistance, and Ms. K. Nakamura and M. Ohnishi for secretarial assistance. We are grateful to Dr. A. Oue and Ms. A. Morita for suggestions and encouragement during the course of this study. This study was supported by a grant to R.K. and M.H. from the “National Institute for Physiological Sciences (NIPS), Joint Research project” and by a grant to E.K. from the Research on Health Sciences focusing on Drug Innovation program of the Japan Health Science Foundation. T.M. was also supported by the Health and Labour Science Research Grants of the Ministry of Health, Labour, and Welfare (Research on Biological Resources) and the Takeda Science and the Nakatomi Foundation.

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Correspondence to Takashi Murakami.

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Ryosuke Kaneko and Atsuko Sato have contributed equally to this work.

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Kaneko, R., Sato, A., Hamada, S. et al. Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT). Transgenic Res 25, 413–424 (2016). https://doi.org/10.1007/s11248-016-9939-3

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  • DOI: https://doi.org/10.1007/s11248-016-9939-3

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