建立c-maf條件性剔除構成物來產生c-Maf剔除小鼠

Abstract

轉錄因子c-Maf調控第二型輔助T淋巴細胞(TH2)的IL-4、第十七型輔助T淋巴細胞(TH17)的IL-21以及第一型調節T細胞(Tr1)的IL-10表現。這些細胞激素對於個別細胞族群除了有重要的功能外，同時也是維持該細胞族群不可或缺的因子。由於c-Maf剔除小鼠於胚胎時期或是出生後幾天內死亡，因此沒有一個好的c-maf基因缺失的動物模式來探討c-Maf缺失對於體內免疫功能的影響。至目前為止，將c-Maf剔除小鼠的fetal liver轉殖進入RAG-1剔除小鼠，是現今可以得到c-Maf剔除T淋巴細胞的方法，可是無法持續繁殖此類實驗鼠。因此，使用條件性基因剔除小鼠是一個解決此問題的最好策略。在本篇論文中，利用DNA recombineering方式建構c-maf條件性剔除構成物。將進一步以此構成物來建立c-Maf條件性剔除小鼠，這將是一個相當有價值的小鼠模式來研究c-Maf在免疫功能中所扮演的角色。

The transcription factor c-Maf is an important transactivator for the IL-4, IL-21 and IL-10 production in TH2, TH17 and Tr1 (Type 1 regulatory T cells), respectively. These cytokines are important for the function of their cell subtypes. Convention c-Maf-deficient mice die within few days after birth. Therefore, there is obstacle to use c-Maf-deficient mice for studying c-Maf regulating immune fuction in vivo. Until now, the only way to investigate the effect of c-Maf deficiency in T cells was transferring the fetal liver of c-Maf null mice into RAG-1 knockout mice. However, these mice can not be propagated to maintain mice strain. The best strategy to study the role of c-Maf in T cells is to generate c-Maf conditional knockout mice. In these study, we built a c-Maf conditional knockout construct by DNA recombineering for generating c-Maf conditional knockout mice. It could be a valuable murine model for the studies of c-Maf mediated immune function.