Mast cell-deficient W-sash c-kit mutant KitW-sh/W-sh mice as a model for investigating mast cell biology in vivo
Mast cell-deficient W-sash c-kit mutant KitW-sh/W-sh mice as a model for investigating mast cell biology in vivo
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DOI：
10.1016/s0002-9440(10)62055-x
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发表时间：
2005-09-01
影响因子：
6
通讯作者：
Galli, SJ
中科院分区：
文献类型：
--
作者：
Grimbaldeston, MA;Chen, CC;Galli, SJ
在白色斑点（W）基因座（即c-kit）中携带某些突变的小鼠表现出c-kit酪氨酸激酶依赖性信号传导减少，导致肥大细胞缺乏和其他表型异常。Kit（W/W-v）小鼠中的c-kit突变损害黑素生成并导致贫血、不育和组织肥大细胞水平显著降低。相反，携带W-sash（W-sh）倒位突变的Kit（W-sh/W-sh-5h）小鼠具有肥大细胞缺乏症，但没有贫血和不育。我们报告说，成年Kit（W-sh/W-sh）小鼠有一个深刻的缺陷，肥大细胞在所有组织检查，但其他分化的造血和淋巴细胞的主要类别的正常水平。与Kit（W/W-v）小鼠不同，Kit（W-sh/W-sh）小鼠在肠道中具有正常数量的TCR γ δ上皮内淋巴细胞，并且没有表现出特发性皮炎、溃疡或胃鳞状乳头状瘤的高发病率，但与Kit（W/W-v）小鼠一样，它们在肠道中缺乏Cajal间质细胞，并且表现出胆汁回流到胃中。通过静脉内、腹膜内或皮内注射野生型骨髓来源的培养肥大细胞，在未辐照的成年Kit（W-sh/W-sh）小鼠中实现肥大细胞群体的全身或局部重建，但不通过移植野生型骨髓细胞。因此，Kit（W-sh/W-sh）小鼠代表了肥大细胞研究的有用模型，特别是用于分析体内肥大细胞功能。
Mice carrying certain mutations in the white spotting (W) locus (ie, c-kit) exhibit reduced c-kit tyrosine kinase-dependent signaling that results in mast cell deficiency and other phenotypic abnormalities. The c-kit mutations in Kit(W/W-v) mice impair melanogenesis and result in anemia, sterility, and markedly reduced levels of tissue mast cells. In contrast, Kit(W-sh/W-sh-5h) mice, bearing the W-sash (W-sh) inversion mutation, have mast cell deficiency but lack anemia and sterility. We report that adult Kit(W-sh/W-sh) mice had a profound deficiency in mast cells in all tissues examined but normal levels of major classes of other differentiated hematopoietic and lymphoid cells. Unlike Kit(W/W-v) mice, Kit(W-sh/W-sh) mice had normal numbers of TCR gamma delta intraepithelial lymphocytes in the intestines and did not exhibit a high incidence of idiopathic dermatitis, ulcers, or squamous papillomas of the stomach, but like Kit(W/W-v) mice, they lacked interstitial cells of Cajal in the gut and exhibited bile reflux into the stomach. Systemic or local reconstitution of mast cell populations was achieved in non-irradiated adult Kit(W-sh/W-sh) mice by intravenous, intraperitoneal, or intradermal injection of wild-type bone marrow-derived cultured mast cells but not by transplantation of wild-type bone marrow cells. Thus, Kit(W-sh/W-sh) mice represent a useful model for mast cell research, especially for analyzing mast cell function in vivo.