Memory and learning disorder analysis using mutation mouse for mental retadation related gene ATRX and elucidation of the genetic control abnormality.

使用智力迟缓相关基因 ATRX 突变小鼠进行记忆和学习障碍分析，并阐明遗传控制异常。

基本信息

批准号：
15500210
负责人：
KITAJIMA Isao
金额：
$ 2.37万
依托单位：
TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

The causative gene of the ATRX syndrome, which maps on chromosome X and shows such phenotypes as mental retardation and α thalassemia, is clarified. It has been reported that intelligence is lowered when exon 2 is mutated. Then, in cooperation with Dr.En Li and Dr.H.Beppu (Harvard University, USA), we performed back-crossing in the C57BL6 mouse system from the 129 mouse system to six generations (N6) in order to produce the ATRX mutant mouse for behavioral analysis. Using the C75BL6, N6 generation mouse, the following results were obtained over the two-year research period from 2003 to 2004. (1) The mutant mice have kock in highly Lac Z gene at the mutation site. The Lac Z gene was well observed in the hippocampus, cerebral cortex and cerebellum by X-gal staining. (2) Immunostaining was carried out with an antibody that recognized the C-terminus of ATRX. As a result, in comparison with the wild type, the low expression of the ATRX protein in the cerebral cortex, cerebellum, and hippoca … More mpus was recognized in the ATRX mutant mouse. (3) Using the antibody that recognized the C-terminus of ATRX, the mutant mouse showed decreased protein expression of approximately 50% in brain tissues by Western blot, in comparison with the wild type. (4) It is well known that the hippocampus controls memory and learning. Therefore, in order to analyze its function, we examined spatial memory learning with the Morris water maze test, and found that memory and learning capability of the mutant mouse were inferior to those of the wild type. This finding was confirmed in the diet remuneration test under the environment which removed aquaphobia. We also performed the open field test and the home cage activity test in order to examine other behavioral disorders of the mutant mouse. From these tests, we noted hyperactivity in the mutant mouse. Although it was affected by bright light in the wild type mouse, the sojourn time in the light-dark environment was reversed in the mutant mouse. The behavioral analysis revealed that the ATRX mutant mouse presented with low learning capability, photophobia sensitivity and hyperactivity. Less

阐明了ATRX综合征的严重基因，该基因在染色体X染色体上绘制并显示了诸如智力低下和αthalassyalsya之类的表型。据报道，当外显子2突变时，智力会降低。然后，与En Li和H. Beppu博士（美国哈佛大学）合作，我们在C57BL6小鼠系统中进行了反向，从129小鼠系统到六代（N6），以产生ATRX突变小鼠进行行为分析。使用C75BL6，N6生成的小鼠，在2003年至2004年的两年研究期间获得了以下结果。（1）突变小鼠在突变位点高度LAC Z基因的骨骼。 X-Gal染色在海马，脑皮质和小脑中很好地观察到了Lac Z基因。（2）用识别ATRX的C末端的抗体进行免疫染色。结果，与野生型相比，ATRX蛋白在脑皮质，小脑和河马中的低表达……在ATRX突变小鼠中识别出更多的MPU。（3）使用识别ATRX的C末端的抗体，与野生型相比，通过Western印迹显示的突变小鼠在脑组织中大约50％的蛋白质表达降低。（4）众所周知，海马控制着记忆和学习。因此，为了分析其功能，我们通过莫里斯水迷宫检验检查了空间记忆学习，并发现突变小鼠的记忆和学习能力不如野生型。这一发现在消除水生植物的环境下的饮食重新测试中得到了证实。我们还进行了开放式测试和家用笼子活性测试，以检查突变小鼠的其他行为障碍。从这些测试中，我们注意到突变小鼠中的多动症。尽管它受到野生型小鼠的明亮光的影响，但在突变小鼠中，浅黑暗环境中的逗留时间却被逆转。行为分析表明，ATRX突变小鼠的学习能力低，恐惧症敏感性和多动症。较少的