A candidate gene of Alzheimer diseases was mutated in senescence-accelerated mouse prone (SAMP) 8 mice
A candidate gene of Alzheimer diseases was mutated in senescence-accelerated mouse prone (SAMP) 8 mice
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DOI：
10.1016/j.bbrc.2021.07.095
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发表时间：
2021-08-04
影响因子：
3.1
通讯作者：
Isobe, Masaharu
中科院分区：
文献类型：
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作者：
Akbor, Maruf Mohammad;Kim, Juhyon;Isobe, Masaharu
衰老加速型小鼠（SAMP）8品系在2月龄时表现出与年龄相关的学习和记忆缺陷（LMD）。我们发现SAMP 8品系的12号染色体位点与学习记忆缺陷（LMD）表型有很强的关联。在寻找候选基因的过程中，我们在SAMP 8 12号染色体LMD上发现了溶质载体家族24钠/钾/钙交换器成员4（Slc 24 a4），该成员具有一个单核苷酸多态性，导致413位的苏氨酸被蛋氨酸取代。由于SLC 24 A4已被假定为晚发性阿尔茨海默病（LOAD）的候选人，我们进一步分析这种多态性的功能重要性。通过在HEK 293细胞中表达Slc 24 a4蛋白，在此我们显示多态性SAMP 8型Slc 24 a4-T413 M与野生型小鼠（Slc 24 a4-WT）相比导致细胞中钙离子（Ca 2+）转运体活性的显著损失。然而，还没有研究显示人类SLC 24 A4多态性与LOAD发病机制的任何功能关联。因此，我们目前的发现可能有助于进一步阐明这种离子交换剂与年龄相关的认知功能障碍的重要性。(C)2021年，任作家。爱思唯尔公司出版
The senescence-accelerated mouse prone (SAMP) 8 strain exhibits age-related learning and memory deficits (LMD) at 2 months of age. We have found strong association of chromosome 12 locus with learning memory deficit (LMD) phenotype in SAMP8 strain. In the course of searching candidate gene, here we identified solute carrier family 24 sodium/potassium/calcium exchanger member 4 (Slc24a4) in SAMP8 chromosome 12 LMD possessing one single nucleotide polymorphism causing amino acid replacement of Threonine at 413 position with Methionine. Since SLC24A4 has been postulated as a candidate of late onset Alzheimer's diseases (LOAD), we further analyze the functional importance of this polymorphism. By expressing Slc24a4 protein in HEK293 cells, here we showed polymorphic SAMP8 type Slc24a4-T413 M causing significant loss of calcium ion (Ca2+ ) transporter activity in cells compared with that of wild type mouse (Slc24a4-WT). However, no study yet shows any functional association of human SLC24A4 polymorphism with the onset of LOAD pathogenesis. Thus, our present finding may further help to clarify the importance of this ion exchanger with age related cognitive dysfunction. (C) 2021 The Authors. Published by Elsevier Inc.