Gfi1 and Gfi1b act equivalently in haematopoiesis, but have distinct, non-overlapping functions in inner ear development
Gfi1 and Gfi1b act equivalently in haematopoiesis, but have distinct, non-overlapping functions in inner ear development
复制标题
DOI：
10.1038/sj.embor.7400618
复制
发表时间：
2006-03-01
期刊：
影响因子：
7.7
通讯作者：
Möröy, T
中科院分区：
文献类型：
--
作者：
Fiolka, K;Hertzano, R;Möröy, T
Gfi1是造血和内耳发育所必需的转录抑制因子。它与其同源物Gfi1b共享一个氨基末端SNAG抑制结构域和六个羧基末端锌指基序，但与Gfi1b不同的是，这些结构域的序列分离不同。在这里，我们描述了两种敲入小鼠模型，其中n端SNAG阻遏物结构域发生突变或Gfi1编码区被Gfi1b取代。没有完整SNAG结构域的小鼠突变体显示Gfi1缺失小鼠的完整表型。然而，Gfi1: Gfi1b敲入小鼠显示几乎正常的前t细胞和中性粒细胞发育，但缺乏适当形成的内耳毛细胞。因此，我们的研究结果表明，完整的SNAG结构域对于Gfi1的所有功能都是必不可少的，并且Gfi1b可以在造血功能上取代Gfi1，但令人惊讶的是，在内耳毛细胞发育中却没有，这表明Gfi1和Gfi1b具有等效的和依赖于结构域的细胞类型特异性功能。
Gfi1 is a transcriptional repressor essential for haematopoiesis and inner ear development. It shares with its paralogue Gfi1b an amino-terminal SNAG repressor domain and six carboxy-terminal zinc-finger motifs, but differs from Gfi1b in sequences separating these domains. Here, we describe two knock-in mouse models, in which the N-terminal SNAG repressor domain was mutated or in which the Gfi1 coding region was replaced by Gfi1b. Mouse mutants without an intact SNAG domain show the full phenotype of Gfi1 null mice. However, Gfi1: Gfi1b knock-in mice show almost normal pre-T-cell and neutrophil development, but lack properly formed inner ear hair cells. Hence, our findings show that an intact SNAG domain is essential for all functions of Gfi1 and that Gfi1b can replace Gfi1 functionally in haematopoiesis but, surprisingly, not in inner ear hair cell development, demonstrating that Gfi1 and Gfi1b have equivalent and domain-dependent, cell type-specific functions.