Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT)
Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT)
复制标题
DOI：
10.1007/s11248-016-9939-3
复制
发表时间：
2016-02
影响因子：
3
通讯作者：
R. Kaneko;Atsuko Sato;S. Hamada;T. Yagi;I. Ohsawa;M. Ohtsuki;E. Kobayashi;M. Hirabayashi;Takashi Murakami
中科院分区：
文献类型：
--
作者：
R. Kaneko;Atsuko Sato;S. Hamada;T. Yagi;I. Ohsawa;M. Ohtsuki;E. Kobayashi;M. Hirabayashi;Takashi Murakami
儿童期皮炎是儿童最常见的皮肤病之一。尽管已经有了各种反映皮炎方面的小鼠模型，但仍然需要一种在儿童时期发生皮炎的动物模型，并且更适合进行组织移植实验。越来越多的证据表明，皮炎患者外周血中的T淋巴细胞显著增强了端粒酶活性。在这里，我们培育了表达端粒酶逆转录酶(TERT)的转基因(TG)大鼠，该大鼠在童年时自发地发生湿疹皮肤炎症。新生TERT-TG大鼠56.5%出现明显皮炎，皮损显微镜下可见海绵样变和棘皮病，伴有淋巴细胞、嗜酸性粒细胞和肥大细胞的浸润。与非皮炎的TERT-TG大鼠相比，有皮炎的TERT-TG大鼠的CD4(2.5倍)和CD8(5倍)T细胞数量增加。皮炎阳性的TERT-TG大鼠外周淋巴细胞中的TERT活性高于非皮炎的TERT-TG大鼠。RT-PCR分析显示，皮炎阳性TERT-TG大鼠脾组织中IL-4水平显著升高，皮炎皮损中干扰素-γ水平明显升高。此外，将患有皮炎的TERT-TG大鼠的皮肤移植到T细胞缺陷的裸鼠身上，表明炎症的皮肤病变无法维持。综上所述，T淋巴细胞中TERT的激活是皮炎的潜在易感因素之一。此外，我们的结果表明，TERT-TG大鼠反映了人类儿童期皮炎的某些方面，这些动物代表了研究儿童期皮炎的潜在动物模型系统。
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.