Identification and functional analysis of genes for learning and memory dysfunction by using Senescence Accelerating Mouse

利用衰老加速小鼠鉴定学习记忆功能障碍基因并进行功能分析

基本信息

批准号：
16310133
负责人：
ISOBE Masaharu
金额：
$ 10.57万
依托单位：
University of Toyama
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16310133/
关键词：
SAM P8 JF1 QTL analysis Learning and Memory Dysfunction Senescence

项目摘要

1) We have obtained F2 mice by mating P8 strain of Senescence Accelerated Mouse (SAMP8) exhibiting age related learning and memory dysfunction with Japanese wild mouse derived JF1 strain showing normal phenotype. We have performed genome-wide QTL analysis on these F2 mice at the age of 5 month by Step Through experiment with more than 120 genetic markers, and found four significant QTL loci on chromosomes 1, 13 and 15. Interestingly, while the candidate loci on Chromosomes 1 and 13 were derived from SAMP8 background, two loci on chromosome 15 were found to be from JF1 background despite it was used as normal control.2) Three speed-congenic strains carrying either SAMP8 derived chromosomes 1, 13, or 15 in JF1 background were established by backcrossing F1 strain with JF1 strain.3) By exhaustive analysis of each candidate regions, we found 3 and 1 genes on chromosomes 1 and 13 carry polymorphisms whose amino acid replacements were specific to the SAM strain, respectively. In 2 loci on chromosome 15, we found 7 and 2 genes carrying polymorphisms associated with amino acid replacements in JF1 strain, respectively.4) The SAM strain specific polymorphism on chromosome 13 was found in a gene coding for an ion channel. When this gene was expressed in cultured cells, we found difference in ion permeability compared with normal control by patch clump methods. This difference suggests the involvement of the ion channel in learning and memory dysfunction although further characterizations are needed.

1）我们通过与日本野生小鼠衍生的JF1菌株的年龄相关学习和记忆功能障碍的衰老加速小鼠（SAMP8）的P8菌株（SAMP8）获得了F2小鼠。 We have performed genome-wide QTL analysis on these F2 mice at the age of 5 month by Step Through experiment with more than 120 genetic markers, and found four significant QTL loci on chromosomes 1, 13 and 15. Interestingly, while the candidate loci on Chromosomes 1 and 13 were derived from SAMP8 background, two loci on chromosome 15 were found to be from JF1 background despite it was used as normal control.2) Three通过对每个候选区域的详尽分析，通过将F1菌株与JF1菌株进行反向交叉菌株建立，在JF1背景中携带SAMP8衍生的染色体1、13或15的速度 - 综合菌株，我们发现染色体上的3和1基因1和13染色体1和13的基因，其1和13均具有氨基酸含量的氨基酸含量，其氨基酸含量是分别针对SAM菌株的相应的。在15号染色体上的2个基因座中，我们发现7和2个基因分别在JF1菌株中携带与氨基酸替代相关的多态性。4）在ION通道的基因编码中发现了SAM菌株13染色体上的SAM菌株特异性多态性。当该基因在培养的细胞中表达时，我们发现与通过斑块结块方法进行正常对照相比，我们发现离子渗透性差异。这种差异表明，尽管需要进一步的特征，但由于需要进一步的特征，因此离子通道参与学习和记忆功能障碍。