Generation of a conditional knockout allele for mammalian Spen protein Mint/SHARP
Generation of a conditional knockout allele for mammalian Spen protein Mint/SHARP
复制标题
DOI：
10.1002/dvg.20296
复制
发表时间：
2007-05
期刊：
影响因子：
1.5
通讯作者：
D. Yabe;Hitoshi Fukuda;Misayo Aoki;S. Yamada;S. Takebayashi;R. Shinkura;Norio Yamamoto;T. Honjo
中科院分区：
文献类型：
--
作者：
D. Yabe;Hitoshi Fukuda;Misayo Aoki;S. Yamada;S. Takebayashi;R. Shinkura;Norio Yamamoto;T. Honjo
Spen蛋白家族存在于蠕虫、苍蝇和哺乳动物中，并且涉及从胚胎发生到衰老的多种生物过程。Spen蛋白具有三个N末端RNA识别基序和一个C末端SPOC结构域。哺乳动物Spen蛋白Mint及其人类直系同源物SHARP与Notch信号传导介质RBP‐J以及Msx 2和几种未配体的核激素受体相互作用，并通过SPOC结构域招募辅阻遏物来赋予这些分子转录抑制活性。尽管有这些体外研究结果，Mint/SHARP的生理作用在很大程度上是未知的，因为Mint种系敲除是胚胎致死的。为了分析出生后小鼠中的Mint/SHARP功能，我们创建了允许Cre/loxP介导的Mint条件性敲除的Mint-floxed小鼠。我们分析了Notch依赖性脾B淋巴细胞发育过程中Mint和RBP-J的上位性，发现Mint通过RBP-J抑制Notch信号传导。此外，薄荷缺乏导致出生后大脑严重发育不全，这表明它可能调节神经细胞的存活。创世纪45：300-306，2007。© 2007 Wiley利斯公司
The Spen protein family is found in worms, flies, and mammals, and is implicated in diverse biological processes from embryogenesis to aging. Spen proteins have three N‐terminal RNA recognition motifs and a C‐terminal SPOC domain. The mammalian Spen proteins Mint and its human ortholog SHARP interact with the Notch‐signaling mediator RBP‐J as well as Msx2 and several unliganded nuclear hormone receptors, and impart transcription‐repressing activity to these molecules by recruiting corepressors through the SPOC domain. Despite these in vitro findings, Mint/SHARP's physiological role is largely unknown, because Mint germline knockouts are embryonic lethal. To analyze Mint/SHARP function in postnatal mice, we created Mint‐floxed mice that allow the Cre/loxP‐mediated conditional knockout of Mint. We analyzed Mint and RBP‐J epistasis during Notch‐dependent splenic B‐lymphocyte development, and found that Mint suppresses Notch signaling through RBP‐J. In addition, Mint deficiency caused severe hypoplasia in postnatal brain, suggesting it may regulate neuronal cell survival. genesis 45:300–306, 2007. © 2007 Wiley‐Liss, Inc.