Attractin Gene Deficiency in Rats Leads to Impairments in Both Activity and Spatial Learning and Memory
Attractin Gene Deficiency in Rats Leads to Impairments in Both Activity and Spatial Learning and Memory
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大鼠吸引素基因缺陷导致活动和空间学习记忆受损
DOI：
10.1016/j.neuroscience.2021.05.006
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发表时间：
2021-05-27
期刊：
影响因子：
3.3
通讯作者：
Zhang, Wei-Ning
中科院分区：
文献类型：
--
作者：
Li, Xiao-Hui;Xue, Cheng;Zhang, Wei-Ning
Attractin（ATRN）是一种广泛分布于大脑中的常染色体隐性基因，参与多种脑功能的执行，并与某些神经精神疾病相关。在这里，我们介绍了一种新的大鼠品系，该品系在ATRN中携带突变，该突变是通过CRISPR/Cas9系统敲入ATRN-G505 C产生的。我们评估了这些突变体ATRN基因敲入大鼠的行为表现。将G505 C突变引入外显子9，并将合成引物插入内含子8-9用于基因分型。第505个氨基酸，Gly（G）残基，突变为Cys（C）残基，即，GGC突变为TGC。行为学实验表明，与野生型大鼠相比，纯合子ATRN大鼠在Morris水迷宫（MWM）中的获取实验中花费更多的时间寻找逃避平台，在探测实验中花费更少的时间在目标区域，在旷场实验（OFT）中行走的距离更短。Western blot和免疫组化结果显示，ATRN基因突变组大鼠脑源性神经营养因子（BDNF）的表达明显减少。总之，我们的研究结果表明，ATRN基因突变直接导致学习和记忆障碍和轻微的运动缺陷。这些发现为突变型ATRN诱导神经退行性改变的机制提供了新的线索。(c)2021年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Attractin (ATRN), an autosomal recessive gene that is widely distributed in the brain, is involved in the execution of a variety of brain functions and associated with certain neuropsychiatric disorders. Here, we intro-duce a novel rat strain harboring a mutation in ATRN that was generated by knocking in ATRN-G505C via the CRISPR/Cas9 system. We assessed the behavioral performance of these mutant ATRN knock-in rats. The G505C mutation was introduced into exon 9, and a synthetic primer was inserted into introns 8-9 for genotyping. The 505th amino acid, a Gly (G) residue, was mutated to a Cys (C) residue, i.e., GGC was mutated to TGC. Behav-ioral experiments showed that homozygous ATRN rats spent significantly more time searching for the escape platform in the acquisition trial and significantly less time in the target area in the probe trial in the Morris water maze (MWM) test and traveled a significantly shorter distance in the open field test (OFT) than wild-type rats. In addition, Western blot analysis and immunohistochemistry showed that rats with the mutant ATRN gene exhib-ited significantly reduced expression of brain-derived neurotrophic factor (BDNF). In summary, our results indi-cate that mutations in the ATRN gene directly lead to learning and memory impairments and slight motor deficits. These findings provide new clues for the mechanism by which mutant ATRN induces neurodegenerative changes.(c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.