Department of Pharmacy, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Gunma, Japan.
Mol Cell Biol. 2014 May;34(10):1812-26. doi: 10.1128/MCB.01524-13. Epub 2014 Mar 10.
Although previous studies have shown that GATA1 is required for mast cell differentiation, the effects of the complete ablation of GATA1 in mast cells have not been examined. Using conditional Gata1 knockout mice (Gata1(-/y)), we demonstrate here that the complete ablation of GATA1 has a minimal effect on the number and distribution of peripheral tissue mast cells in adult mice. The Gata1(-/y) bone marrow cells were capable of differentiating into mast cells ex vivo. Microarray analyses showed that the repression of GATA1 in bone marrow mast cells (BMMCs) has a small impact on the mast cell-specific gene expression in most cases. Interestingly, however, the expression levels of mast cell tryptases in the mouse chromosome 17A3.3 were uniformly reduced in the GATA1 knockdown cells, and GATA1 was found to bind to a 500-bp region at the 5' end of this locus. Revealing a sharp contrast to that observed in the Gata1-null BMMCs, GATA2 deficiency resulted in a significant loss of the c-Kit(+) FcεRIα(+) mast cell fraction and a reduced expression of several mast cell-specific genes. Collectively, GATA2 plays a more important role than GATA1 in the regulation of most mast cell-specific genes, while GATA1 might play specific roles in mast cell functions.
尽管先前的研究表明 GATA1 是肥大细胞分化所必需的，但尚未研究 GATA1 完全缺失对肥大细胞的影响。使用条件性 Gata1 敲除小鼠（Gata1(-/y)），我们在此证明 GATA1 的完全缺失对成年小鼠周围组织肥大细胞的数量和分布的影响很小。Gata1(-/y) 骨髓细胞能够在体外分化为肥大细胞。微阵列分析表明，在大多数情况下，GATA1 在骨髓肥大细胞（BMMC）中的抑制对肥大细胞特异性基因表达的影响很小。然而，有趣的是，在 GATA1 敲低细胞中，鼠 17A3.3 号染色体上的肥大细胞 tryptase 的表达水平均匀降低，并且发现 GATA1 与该基因座 5'端的 500bp 区域结合。与在 Gata1 缺失的 BMMC 中观察到的情况形成鲜明对比的是，GATA2 缺陷导致 c-Kit(+) FcεRIα(+) 肥大细胞亚群的显著丢失和几个肥大细胞特异性基因的表达降低。总的来说，GATA2 在调节大多数肥大细胞特异性基因方面比 GATA1 发挥更重要的作用，而 GATA1 可能在肥大细胞功能中发挥特定作用。
