Chymase-Cre; Mcl-1fl/fl Mice Exhibit Reduced Numbers of Mucosal Mast Cells
Chymase-Cre; Mcl-1fl/fl Mice Exhibit Reduced Numbers of Mucosal Mast Cells
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DOI：
10.3389/fimmu.2019.02399
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发表时间：
2019-10-15
影响因子：
7.3
通讯作者：
Siebenhaar, Frank
中科院分区：
文献类型：
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作者：
Luo, Ying;Meyer, Nicole;Siebenhaar, Frank
肥大细胞（MC）被认为是诱发过敏症状的关键效应细胞，并且它们是先天性和适应性免疫应答的重要参与者。在小鼠中，已经描述了两种主要类型的MC：结缔组织MC（CTMC）和粘膜MC（MMCs）。然而，由于缺乏合适的动物模型来研究体内的基质金属细胞，因此对基质金属细胞的生物学功能知之甚少。在这里，我们的目的是产生一个选择性缺乏MMC的小鼠模型。先前已经描述了在狒狒α-糜酶启动子的控制下表达的Cre主要定位于MMC中。因此，我们将α-糜酶-Cre转基因小鼠与携带髓细胞白血病序列1（Mcl-1）的floxed等位基因的小鼠交配。Mcl-1编码MC中的细胞内抗凋亡因子;因此，预期MMC中的选择性减少。我们的研究结果表明，这种新的小鼠模型包含粘膜组织中的MMC数量显着减少，而CTMCs的数量是正常的。因此，Chm-Cre; Mcl-1（fl/fl）小鼠是研究体内MMC病理生理功能的有用工具。
Mast cells (MCs) are considered as key effector cells in the elicitation of allergic symptoms, and they are essential players in innate and adaptive immune responses. In mice, two main types of MCs have been described: connective tissue MCs (CTMCs) and mucosal MCs (MMCs). However, little is known about the biological functions of MMCs, which is due to the lack of suitable models to investigate MMCs in vivo. Here, we aimed to generate a mouse model selectively deficient in MMCs. It has been previously described that Cre expressed under the control of the baboon alpha-chymase promotor is predominantly localized in MMCs. Therefore, we mated alpha-chymase-Cre transgenic mice with mice bearing a floxed allele of the myeloid cell leukemia sequence 1 (Mcl-1). Mcl-1 encodes for an intracellular antiapoptotic factor in MCs; hence, a selective reduction in MMCs was expected. Our results show that this new mouse model contains markedly reduced numbers of MMCs in mucosal tissues, whereas numbers of CTMCs are normal. Thus, Chm-Cre; Mcl-1(fl/fl) mice are a useful tool for the investigation of the pathophysiological functions of MMCs in vivo.