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Characterization of floor plate specific genes by using transgenic mice

使用转基因小鼠表征底板特定基因

基本信息

批准号：
12480235
负责人：
MASU Masayuki
金额：
$ 8.32万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

Floor plate, a group of non-neural cells located in the ventral midline of the developing nervous system, plays an important role in neural patterning by secreting morphogens and axon guidance molecules. This study aims to clarify the functional significance of two floor plate specific genes, sulfatase FP1 (SulfFP1) and Autotaxin by using transgenic mice.SulfFP1 is a novel member of the sulfatase family, and is expressed in the floor plate, choroid plexus, bone-forming regions, kidney, some neurons in the adult brain. To characterize the regulatory element of SulfFP1 expression in these tissues, transgenic mice harboring the green fluorescent protein (GFP) under the control of the SulfFP1 promoter were generated. The 12 kbp genomic sequence upstream of the SulfFP1 transcription initiation site drives GFP expression in bone-formmg regions, kidney, and adult brain, but not in the floor plate and choroid plexus. Upstream 2.3 kbp sequence, but not 1.8 kbp sequence, drives the similar expression in the bone-formmg regions. The sequence between 1.8 kbp and 2.3 kbp includes the consensus sequence for the Sox-binding that is essential for bone development.Autotaxin, a member of the ecto-/exo-phosphodiesterase family, is initially identified as a cell motility promoting factor. It is recently reported to possess the lysophospholipase D activity that is required lysophophatidic acid production in the extracellular space, although its physiological role remains unknown. We therefore tried to generate transgenic mice that are overexpressing Autotaxin in the body, but only weakly-expressing lines were obtained. Slight increase of oligodendrocytes in the brain and spinal cord were observed in these lines. These results indicate that Autotaxin is involved in the oligodendrocyte differentiation, and that Autotaxin overexpression may lead to lethal phenotype in the early development.

底板是一组位于发育中神经系统腹侧中线的非神经细胞，通过分泌形态发生素和轴突引导分子在神经模式形成中发挥重要作用。本研究旨在通过转基因小鼠阐明硫酸酯酶FP1（SulfFP1）和自分泌运动因子这两个底板特异性基因的功能意义。SulfFP1是硫酸酯酶家族的新成员，在底板、脉络丛、成骨区、肾脏、成人大脑的一些神经元中表达。为了表征这些组织中 SulfFP1 表达的调控元件，产生了在 SulfFP1 启动子控制下携带绿色荧光蛋白 (GFP) 的转基因小鼠。 SulfFP1 转录起始位点上游的 12 kbp 基因组序列驱动 GFP 在骨形成区域、肾脏和成人大脑中表达，但不在底板和脉络丛中表达。上游 2.3 kbp 序列而非 1.8 kbp 序列在骨形成区域中驱动相似的表达。 1.8 kbp 和 2.3 kbp 之间的序列包括骨骼发育所必需的 Sox 结合的共有序列。 Autotaxin 是外切/外切磷酸二酯酶家族的成员，最初被鉴定为细胞运动促进因子。最近有报道称其具有细胞外空间溶血磷脂酸生成所需的溶血磷脂酶 D 活性，但其生理作用仍不清楚。因此，我们尝试培育体内过度表达自分泌运动因子的转基因小鼠，但只获得了弱表达的品系。在这些细胞系中观察到大脑和脊髓中少突胶质细胞的轻微增加。这些结果表明Autotaxin参与少突胶质细胞的分化，并且Autotaxin过度表达可能导致早期发育中的致死表型。