BMPシグナル伝達系の下流転写因子SEF1/SIP-1ファミリーの研究

BMP信号转导系统下游转录因子SEF1/SIP-1家族的研究

• 批准号: 11680678
• 负责人: HIGASHI Yujiro
• 金额: $ 2.37万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680678/
• 关键词: TGFβ; BMP; SMAD; ZFH1; SIP1; δEF1; knockout mouse; mouse development; zfh; BMPシグナル

SIP1, a transcription factor belonging to δEF1/zfh (zinc-finger and homeodomain) family, can interact with the Smad proteins in a TGFβ-dependent manner. To elucidate the role of SIP1 in mouse development, we examined its expression during embryogenesis, and generated the SIP1 KO mouse.At E7.5, SIP1 is widely expressed in mesoderm except for the node and notochord. At E8.5, specific expression is observed in the neural tube and presomitic mesoderm. At later developmental stages, it is expressed in lens epithelium, neural crest derivatives, and dermamyotome. For targeting the SIP1 gene, exon 7 was deleted to truncate most and functional part of the SIP1 protein. Homozygous mutants begin to exhibit abnormal development around E8.25. Notochord and somites appear to be severely affected and not properly formed. The mutant embryos also display defects in neural tube closure, and fail to turn. We will investtigate the role of SIP1 in the notochord, somite, and neural tube formation.

SIP1是δEF1/zfh （zinc-finger and homeodomain）家族的转录因子，可以通过tgf β依赖的方式与Smad蛋白相互作用。为了阐明SIP1在小鼠发育中的作用，我们检测了其在胚胎发生过程中的表达，并产生了SIP1 KO小鼠。在E7.5时，除淋巴结和脊索外，SIP1在中胚层广泛表达。在E8.5时，在神经管和体前中胚层中观察到特异性表达。在发育后期，它在晶状体上皮、神经嵴衍生物和真皮组织中表达。为了靶向SIP1基因，删除了外显子7，截断了SIP1蛋白的大部分和功能部分。纯合突变体在E8.25左右开始表现出异常发育。脊索和有时似乎受到严重影响，并没有正确形成。突变胚胎也表现出神经管闭合缺陷，不能转动。我们将探讨SIP1在脊索、体体和神经管形成中的作用。

项目成果

Moribe, H., Takagi, T., Kondoh, H., and Higashi, Y.: "Suppression of polydactyly of the Gli3 mutant (extra toes) by δEF1 homozygous mutation."Develop.Growth.Differ.. 42. 367-376 (2000)

Moribe, H.、Takagi, T.、Kondoh, H. 和 Higashi, Y.：“δEF1 纯合突变对 Gli3 突变体（额外脚趾）的多指畸形的抑制。”Develop.Growth.Differ.. 42. 367- 376 (2000)

Moribe H.: "Suppression of polydactyly of Gli3 mutant (extra toes) by δEF1 homozygous mutation"Develoment,Growht & Differentiation. (in press). (2000)

Moribe H.：“δEF1 纯合突变对 Gli3 突变体（额外脚趾）的多指畸形的抑制”，发育、生长和分化（印刷中）。

Moribe,H.: "Suppression of polydactyly of the Gli3 mutant (extra toes) by dEF1 homozygous mutation."Develop.Growth.Differ.. 42. 367-376 (2000)

Moribe, H.：“dEF1 纯合突变对 Gli3 突变体（额外脚趾）的多指畸形的抑制。”Develop.Growth.Differ.. 42. 367-376 (2000)

Furusawa,T: "Identification of CtBP1 and CtBP2 as corepressors of zinc finger-homeodomain factor dEF1."Mol.Cell.Biol.. 19. 8581-8590 (1999)

Furusawa,T：“鉴定 CtBP1 和 CtBP2 作为锌指同源域因子 dEF1 的辅阻遏物。”Mol.Cell.Biol.. 19. 8581-8590 (1999)

Furusawa,T: "Identification of CtBP1 and CtBP2 as corepressors of zinc finger-homeodomain factor δEF1"Mol.Cell.Biol.. 19. 8581-8590 (1999)

Furusawa，T：“鉴定 CtBP1 和 CtBP2 作为锌指同源结构域因子 δEF1 的辅阻遏物”Mol.Cell.Biol.. 19. 8581-8590 (1999)