Transgenic mouse approaches to the pathogenesis of hereditary type of human autoimmune disease

我们试图通过一种命运映射策略来监控表达Aire的胸腺髓质上皮细胞(MTECs)的产生和维持。在这种策略中，在Aire调控元件控制下表达Cre重组酶的细菌人工染色体转基因小鼠与GFP报告菌株杂交。我们发现，除了在成熟的mTEC中表达外，Aire还在三个生殖细胞层出现之前的早期胚胎中表达。利用Cre重组酶仅在mTECs中表达的转基因株系，我们发现Aire^+CD80；高表达的mTECs进一步发展到Aire^-CD80；mTECs的中间阶段，这表明Aire的表达从诱导后到细胞死亡不是结构性的，而是在末端分化开始时下调。

We sought to monitor the production and maintenance of Aire-expressing medullary thymic epithelial cells(mTECs) by a fate-mapping strategy in which bacterial artificial chromosome transgenic mice expressing Cre recombinase under the control of the Aire regulatory element were crossed with a GFP reporter strain. We found that, in addition to its well recognized expression within mature mTECs, Aire was expressed in the early embryo before emergence of the three germ cell layers. With the use of one transgenic line in which Cre recombinase expression was confined to mTECs, we found that Aire^+ CD80^<high> mTECs further progressed to an Aire^-CD80^<intermediate> stage, suggesting that Aire expression is not constitutive from after its induction until cell death but instead is down-regulated at the beginning of terminal differentiation.