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首页> 外文期刊>Behavioural Brain Research: An International Journal >Relaxin-3 receptor (Rxfp3) gene knockout mice display reduced running wheel activity: Implications for role of relaxin-3/RXFP3 signalling in sustained arousal
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Relaxin-3 receptor (Rxfp3) gene knockout mice display reduced running wheel activity: Implications for role of relaxin-3/RXFP3 signalling in sustained arousal

机译:Relaxin-3受体(RXFP3)基因敲除小鼠显示减少的运行轮活动:对持续唤醒中的休闲素-3 / RxFP3信号传导的影响

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摘要

Anatomical and pharmacological evidence suggests the neuropeptide, relaxin-3, is the preferred endogenous ligand for the relaxin family peptide-3 receptor (RXFP3) and suggests a number of putative stress-and arousal-related roles for RXFP3 signalling. However, in vitro and in vivo evidence demonstrates exogenous relaxin-3 can activate other relaxin peptide family receptors, and the role of relaxin-3/RXFP3 signalling in specific brain circuits and associated behaviours in mice is not well described. In this study, we characterised the behaviour of cohorts of male and female Rxfp3 gene knockout (KO) mice (C57/B6J(RXFP3TM1/DGen),) relative to wild-type (WT) littermates to determine if this receptor KO strain has a similar phenotype to its ligand KO equivalent. Rxfp3 KO mice displayed similar performance to WT littermates in several acute behavioural paradigms designed to gauge motor coordination (rotarod test), spatial memory (Y-maze), depressive-like behaviour (repeat forced-swim test) and sensorimotor gating (prepulse inhibition of acoustic startle). Notably however, male and female Rxfp3 KO mice displayed robust and consistent (dark phase) hypoactivity on voluntary home-cage running wheels (similar to 20-60% less activity/h), and a small but significant decrease in anxiety-like behavioural traits in the elevated plus maze and light/dark box paradigms. Importantly, this phenotype is near identical to that observed in two independent lines of relaxin-3 KO mice, suggesting these phenotypes are due to the elimination of ligand or receptor and RXFP3-linked signalling. Furthermore, this behavioural characterisation of Rxfp3 KO mice identifies them as a useful experimental model for studying RXFP3-linked signalling and assessing the selectivity and/or potential off-target actions of RXFP3 agonists and antagonists, which could lead to an improved understanding of dysfunctional arousal in mental health disorders, including depression, anxiety, insomnia and neurodegenerative diseases. (C) 2014 Published by Elsevier B.V.
机译:解剖学和药理学证据表明神经肽,松弛素-3是松弛素家族肽-3受体(RXFP3)的优选内源性配体,并表明RXFP3信号传导的许多推定的应力和令人讨厌的作用。然而,体外和体内证据证明外源性弛豫素-3可以激活其他松弛素肽家族受体,并且对小鼠特异性脑电路和相关行为中的弛豫素-3 / RxFP3信号传导的作用也没有很好地描述。在这项研究中,我们表征了相对于野生型(WT)凋落物的雄性和雌性RXFP3基因敲除(C57 / B6J(RXFP3TM1 / DGen),)的行为,以确定该受体KO菌株是否有一个与其配体KO相同的类似表型。 RXFP3 KO小鼠在几种急性行为范式中显示出类似的性能,旨在规范电机协调(Rotarod Test),空间记忆(Y-Maze),抑郁症状行为(重复强制游泳测试)和传感器门控(Prepulse抑制)声学惊吓)。然而,特别是,雄性和雌性RXFP3 KO小鼠在自愿家庭笼车运行轮上显示稳健且一致(黑相)的低管(类似于20-60%的活性/小时),焦虑的行为性状的小而显着降低在升高的加迷宫和光/暗盒范式。重要的是,这种表型接近与两种独立的松弛素-3ko小鼠中观察到的相同,表明这些表型是由于消除配体或受体和RxFP3连接的信号传导。此外,RXFP3 KO小鼠的这种行为表征将它们鉴定为研究RXFP3连接信号传导的有用实验模型,并评估RXFP3激动剂和拮抗剂的选择性和/或潜在的脱靶作用,这可能导致对功能障碍的理解改善在心理健康障碍,包括抑郁,焦虑,失眠和神经变性疾病。 (c)2014由elestvier b.v出版。

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