Trim46 knockout impaired neuronal architecture and caused hypoactive behavior in rats

IF 2 3区 生物学 Q2 ANATOMY & MORPHOLOGY Developmental Dynamics Pub Date : 2024-01-09 DOI:10.1002/dvdy.687
Feifei Guan, Shan Gao, Hanxuan Sheng, Yuanwu Ma, Wei Chen, Xiaolong Qi, Xu Zhang, Xiang Gao, Shuo Pang, Lianfeng Zhang, Li Zhang
{"title":"Trim46 knockout impaired neuronal architecture and caused hypoactive behavior in rats","authors":"Feifei Guan,&nbsp;Shan Gao,&nbsp;Hanxuan Sheng,&nbsp;Yuanwu Ma,&nbsp;Wei Chen,&nbsp;Xiaolong Qi,&nbsp;Xu Zhang,&nbsp;Xiang Gao,&nbsp;Shuo Pang,&nbsp;Lianfeng Zhang,&nbsp;Li Zhang","doi":"10.1002/dvdy.687","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Tripartite motif (TRIM46) is a relatively novel protein that belongs to tripartite motif family. TRIM46 organizes parallel microtubule arrays on the axons, which are important for neuronal polarity and axonal function. TRIM46 is highly expressed in the brain, but its biological function in adults has not yet been determined.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p><i>Trim46</i> knockout (KO) rat line was established using CRISPR/cas9. <i>Trim46</i> KO rats had smaller hippocampus sizes, fewer neuronal dendritic arbors and dendritic spines, and shorter and more distant axon initial segment. Furthermore, the protein interaction between endogenous TRIM46 and FK506 binding protein 5 (FKBP5) in brain tissues was determined; <i>Trim46</i> KO increased hippocampal FKBP5 protein levels and decreased hippocampal protein kinase B (Akt) phosphorylation, gamma-aminobutyric acid type A receptor subunit alpha1 (GABRA1) and glutamate ionotropic receptor NMDA type subunit 1 (NMDAR1) protein levels. <i>Trim46</i> KO rats exhibited hypoactive behavioral changes such as reduced spontaneous activity, social interaction, sucrose preference, impaired prepulse inhibition (PPI), and short-term reference memory.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>These results demonstrate the significant impact of <i>Trim46</i> KO on brain structure and behavioral function. This study revealed a novel potential association of TRIM46 with dendritic development and neuropsychiatric behavior, providing new insights into the role of TRIM46 in the brain.</p>\n </section>\n </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 7","pages":"659-676"},"PeriodicalIF":2.0000,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Developmental Dynamics","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/dvdy.687","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Tripartite motif (TRIM46) is a relatively novel protein that belongs to tripartite motif family. TRIM46 organizes parallel microtubule arrays on the axons, which are important for neuronal polarity and axonal function. TRIM46 is highly expressed in the brain, but its biological function in adults has not yet been determined.

Results

Trim46 knockout (KO) rat line was established using CRISPR/cas9. Trim46 KO rats had smaller hippocampus sizes, fewer neuronal dendritic arbors and dendritic spines, and shorter and more distant axon initial segment. Furthermore, the protein interaction between endogenous TRIM46 and FK506 binding protein 5 (FKBP5) in brain tissues was determined; Trim46 KO increased hippocampal FKBP5 protein levels and decreased hippocampal protein kinase B (Akt) phosphorylation, gamma-aminobutyric acid type A receptor subunit alpha1 (GABRA1) and glutamate ionotropic receptor NMDA type subunit 1 (NMDAR1) protein levels. Trim46 KO rats exhibited hypoactive behavioral changes such as reduced spontaneous activity, social interaction, sucrose preference, impaired prepulse inhibition (PPI), and short-term reference memory.

Conclusions

These results demonstrate the significant impact of Trim46 KO on brain structure and behavioral function. This study revealed a novel potential association of TRIM46 with dendritic development and neuropsychiatric behavior, providing new insights into the role of TRIM46 in the brain.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Trim46 基因敲除会损害大鼠的神经元结构,并导致其行为减退。
背景:三方基序(TRIM46)是属于三方基序家族的一种相对新颖的蛋白质。TRIM46在轴突上组织平行的微管阵列,对神经元的极性和轴突功能非常重要。TRIM46在大脑中高度表达,但其在成人中的生物学功能尚未确定:结果:利用CRISPR/cas9技术建立了Trim46基因敲除(KO)大鼠品系。结果:利用CRISPR/cas9技术建立了Trim46基因敲除(KO)大鼠品系,发现Trim46 KO大鼠的海马体积较小,神经元树突轴和树突棘较少,轴突初段较短且距离较远。此外,还测定了脑组织中内源性TRIM46与FK506结合蛋白5(FKBP5)之间的蛋白相互作用;Trim46 KO增加了海马FKBP5蛋白水平,降低了海马蛋白激酶B(Akt)磷酸化、γ-氨基丁酸A型受体亚基α1(GABRA1)和谷氨酸离子传导受体NMDA型亚基1(NMDAR1)蛋白水平。Trim46 KO 大鼠表现出低度活跃的行为变化,如自发活动减少、社交互动减少、蔗糖偏好减少、前脉冲抑制(PPI)受损以及短期参考记忆减少:这些结果证明了 Trim46 KO 对大脑结构和行为功能的重大影响。这项研究揭示了TRIM46与树突发育和神经精神行为的潜在联系,为TRIM46在大脑中的作用提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Developmental Dynamics
Developmental Dynamics 生物-发育生物学
CiteScore
5.10
自引率
8.00%
发文量
116
审稿时长
3-8 weeks
期刊介绍: Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.
期刊最新文献
Review on pathogenesis and treatment of Alzheimer's disease. Cover Image Issue Information Editorial Editorial highlights
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1