Production of norbin (a novel neurite-outgrowth factor) deficient mouse

Norbin（一种新型神经突生长因子）缺陷型小鼠的生产

基本信息

批准号：
12640670
负责人：
MARUYAMA Kei
金额：
$ 2.24万
依托单位：
Saitama Medical School (2001-2002)Tokyo Metropolitan Organization for Medical Research (2000)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
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

Norbin is a novel gene, which is localized in central and peripheral neurons. Its expression is increased in rat hippocampus slices by the treatment of tetraethylammonium, which induces the facilitation of synaptic transmission as long term potentiation induced by tetanus stimulation. When norbin was overexpressed in Neuro2a cells, neural culture cell line, neurite outgrowth was observed. From these results it was suggested that norbin is related to neural plasticity. Norbin was reported by another group as neurochondrin. Secreted norbin was shown to promote hydroxyapatide resorptive activity of bone marrow cells. Norbin is secreted from COS cells overexpressing it. No signal peptide sequence is observed in that of norbin, and it was secreted as a whole molecule without any processing. The deletion of C-terminal of the middle portion of norbin reduced the secretion. This secretion was not inhibited by brefeldin A. The secretory mechanism is worth for the future study. We could not obtain the homologous recombinant ES cells to make a norbin-deficient mouse. The very low efficiency of the homologous recombination of the norbin gene might be because of the gene structure of norbin. The random insertion strategy performed by a German group produced a norbin deficient mouse by chance. However, the insertion was very near the C-terminal region and this C-terminal region deficient norbin was expressed as much as wild one. No structural or functional changes were observed in the mutant mice. It was concluded that this C-terminal portion of norbin had no significant physiological meanings. The completely deficient mice were necessary for the further study on the physiological function of norbin.

Norbin是一种新型基因，位于中央和周围神经元中。通过治疗四乙基铵，它的表达在大鼠海马切片中增加了，从而诱导突触传播的促进，因为这是由破伤风刺激引起的长期增强。当Norbin在神经2A细胞中过表达时，观察到神经培养细胞系时，神经突生长就会产生。从这些结果提出，诺宾与神经可塑性有关。诺宾（Norbin）由另一组为神经软骨蛋白报道。分泌的诺宾被证明可以促进骨髓细胞的羟基磷灰胺吸收活性。 Norbin是从过表达的COS细胞中分泌的。在Norbin的肽中未观察到信号肽序列，并且它是整个分子而没有任何处理的整个分子。 Norbin中部C末端的删除减少了分泌。 Brefeldin A并未抑制这种分泌。分泌机制对于未来的研究来说是值得的。我们无法获得同源的重组ES细胞来使诺宾缺陷小鼠。 Norbin基因同源重组的效率非常低，可能是由于Norbin的基因结构。德国组执行的随机插入策略偶然产生了诺宾缺乏的小鼠。但是，插入非常接近C末端区域，而该C末端区域不足的Norbin表达了与野生的表达一样多。突变小鼠中未观察到结构性或功能变化。结论是，诺宾的C末端部分没有显着的生理含义。对于诺宾的生理功能的进一步研究，完全缺乏小鼠是必需的。