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

Transgenic Res. 2016 Aug;25(4):413-24. doi: 10.1007/s11248-016-9939-3. Epub 2016 Feb 17.

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.

Keywords: Dermatitis; Telomerase reverse transcriptase (TERT); Transgenic rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dermatitis / etiology*
  • Dermatitis / genetics
  • Dermatitis / pathology
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Rats, Transgenic / genetics*
  • Skin / pathology
  • T-Lymphocytes / physiology
  • Telomerase / genetics*
  • Transgenes

Substances

  • Telomerase
  • Tert protein, rat