School of Veterinary Medicine, Kitasato University, Towada, 034-8628, Japan.
Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan.
Biochem Biophys Res Commun. 2021 Apr 30;551:127-132. doi: 10.1016/j.bbrc.2021.03.025. Epub 2021 Mar 13.
Mast cell-deficient mice are helpful for understanding the roles of mast cells in vivo. To date, a dozen mouse models for mast cell deficiency have been reported. However, mice with a specific depletion of all populations of mast cells have not been reported. We generated knock-in mice, termed Mcpt5/Cma1 mice, expressing human diphtheria toxin A (DT) receptor under the endogenous promoter of Mcpt5 (also known as Cma1), which encodes mouse mast cell protease-5. Flow cytometry and histological analysis showed that intraperitoneal injection of DT induced almost complete depletion of mast cells in heterozygote Mcpt5/Cma1 mice. The deletion rates of mast cells in peritoneal cavity, mesentery, abdominal skin, ear skin, and glandular stomach were 99.9%, 100%, 98.7%, 97.7%, and 100%, respectively. Passive cutaneous anaphylaxis reaction also revealed mast cell deficiency in ear skin after DT treatment. Other than mast cells, a small percentage of marginal zone B cells in Mcpt5/Cma1 mice were killed by DT treatment. In conclusion, the Mcpt5/Cma1 mouse model is valuable for achieving conditional depletion of all populations of mast cells without inducing a marked reduction in other cells.
缺乏肥大细胞的小鼠有助于理解肥大细胞在体内的作用。迄今为止,已经报道了十几种用于肥大细胞缺乏的小鼠模型。然而,尚未报道具有所有肥大细胞群体特异性耗竭的小鼠。我们生成了敲入小鼠,称为 Mcpt5/Cma1 小鼠,其在 Mcpt5(也称为 Cma1)的内源性启动子下表达人白喉毒素 A (DT) 受体,该基因编码小鼠肥大细胞蛋白酶-5。流式细胞术和组织学分析表明,腹腔内注射 DT 可诱导杂合子 Mcpt5/Cma1 小鼠中肥大细胞几乎完全耗竭。腹腔、肠系膜、腹部皮肤、耳部皮肤和胃腺中肥大细胞的缺失率分别为 99.9%、100%、98.7%、97.7%和 100%。DT 处理后,被动皮肤过敏反应也揭示了耳部皮肤中的肥大细胞缺乏。除了肥大细胞外,少量 Mcpt5/Cma1 小鼠的边缘区 B 细胞也被 DT 处理杀死。总之,Mcpt5/Cma1 小鼠模型可用于实现所有肥大细胞群体的条件性耗竭,而不会引起其他细胞的明显减少。