Analysis of expression and function of regulatory molecules in the whole embryos by new developmetnal engineering system

新型发育工程系统分析全胚胎调控分子表达及功能

• 批准号: 08307001
• 负责人: OTANI Hiroki
• 金额: $ 12.99万
• 依托单位: Shimane Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08307001/
• 关键词: exo utero development; knock out mouse; ras; Death-associated protein kinase; mmab; Dnrk; Dmnk; goosecoid; 組織形成; K-ras遺伝子; CaMキナーゼ; 形態形成; ホメオボックス遺伝子; 受容体型チロシンキナーゼ

1. Using exo utero development system, functions of several regulatory molecules in the histogenesis of the organs including brain, adrenal cortex, and joints were elucidated. Introduction of exo utero system to the similar analyzes on the following molecules were designed and have been partially initiated. (Otani)2. K-ras (-/-) mice are embryonic lethal and the embryonic heart has extremely thin wall, whereas H-ras (-/-) and N-ras (-/-) mice appear normal throughout their life span. H-ras (-/-) N-ras (-/-), and H-ras (+/-) N-ras (+/-) K-ras (+/-) mice are viable, suggesting that biallelic expression of K-ras gene or monoallelic expression of both N-ras and K-ras genes are sufficient for mouse development. (Aiba)3. We cloned a rat homologue of the human Death-associated protein kinase (DAP kinase). DAP kinase was expressed in both mantle and ventricular zones of the entire neuraxis on E15. The expression decreased markedly after birth in the brain, but was maintained in several restric … More ted mature neuronal populations, suggesting that DAP kinase is involved partially in the programd neuronal cell death but in other neuronal functions including synaptic plasticity. (Sakagami)4. We identified several candidate Hox gene targets, including a mouse homologue of the C.elegans gene mab21 (mmb). To analyze the function of mmab we generated transgenic mice and prepared antibodies against mmab gene product. (Takahashi)5. We have identified and characterized novel Drosophila protein kinases, Dnrk and Dmnk, expressed specifically in the developing nervous system and in germline during its establishment, respectively. We have also identified and characterized mouse orthologs of Dnrk, mRor1 and mRor2. We are now investigating their functional roles in the development of the nervous system. (Minami)6. We showed that homeobox gene Goosecoid mutant mice display abnormalities in the trachea, appendicular skeleton and external genitalia. Given the similar expression pattern and the knock-out phenotypes of the Goosecoid and Msx1 genes, the double ko mice for them were created. The data imply the presence of some genetic interactions involved in the patterning of middle ear bones. (Yamada) Less

1.利用子宫外发育系统，阐明了几种调控分子在脑、肾上腺皮质和关节等器官组织发生中的作用。将子宫外系统引入到对以下分子的类似分析中，并已部分启动。（大谷）K-ras（-/-）小鼠是胚胎致死的，胚胎心脏具有极薄的壁，而H-ras（-/-）和N-ras（-/-）小鼠在其整个生命周期中表现正常。H-ras（-/-）N-ras（-/-）和H-ras（+/-）N-ras（+/-）K-ras（+/-）小鼠是存活的，表明K-ras基因的双等位基因表达或N-ras和K-ras基因的单等位基因表达对于小鼠发育是足够的。（Aiba）3.我们克隆了人类死亡相关蛋白激酶（DAP激酶）的大鼠同源物。在E15，DAP激酶在整个轴突的套区和脑室区都有表达。出生后大脑中的表达明显下降，但在几个限制性发育中仍保持不变。 ...更多信息 结果表明，DAP激酶部分参与了神经元细胞的程序性死亡，但也参与了包括突触可塑性在内的其他神经元功能。（坂上）4.我们确定了几个候选Hox基因靶点，包括秀丽隐杆线虫基因mab 21（mmb）的小鼠同源物。为了分析mmab的功能，我们制备了转基因小鼠并制备了抗mmab基因产物的抗体。5.我们已经确定和特点的新果蝇蛋白激酶，Dnrk和Dmnk，专门在发育中的神经系统和生殖系在其建立过程中，分别表达。我们还鉴定和表征了Dnrk、mRor 1和mRor 2的小鼠直系同源物。我们现在正在研究它们在神经系统发育中的功能作用。6.我们发现同源异型盒基因Goosecoid突变小鼠在气管、无脊椎骨骼和外生殖器中显示出异常。考虑到Goosecoid和Msx 1基因的相似表达模式和敲除表型，创建了它们的双ko小鼠。这些数据意味着中耳骨的形成与某些遗传相互作用有关。（山田）减

项目成果

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