Behavioral characteristics of ubiquitin-specific peptidase 46-deficient mice.
Behavioral characteristics of ubiquitin-specific peptidase 46-deficient mice.
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DOI：
10.1371/journal.pone.0058566
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ebihara S
中科院分区：
文献类型：
--
作者：
Imai S;Kano M;Nonoyama K;Ebihara S
我们先前已经确定Usp 46，编码泛素特异性肽酶46，作为一个数量性状基因影响小鼠在悬尾试验（TST）和强迫游泳试验中的不动时间。我们鉴定的突变是编码赖氨酸（Lys 92）的3-bp缺失，并且具有该突变的小鼠（MT小鼠）以及Usp 46 KO小鼠表现出较短的TST不动时间。行为药理学表明，γ-氨基丁酸A（GABAA）受体参与调节TST不动时间。为了了解Usp 46在多大程度上控制行为表型，这可能与人类精神障碍有关，我们对Usp 46 MT和KO小鼠进行了多种行为测试，包括旷场测试，乙醇偏好测试，乙醇诱导的翻正反射测试，蔗糖偏好测试，新奇抑制进食测试，大理石掩埋测试和新物体识别测试。尽管Usp 46 MT和KO小鼠的行为表型并不总是相同，但Usp 46的缺乏显着影响了所有这些测试的表现。在旷场试验中，Usp 46 KO小鼠的活性水平低于野生型（WT）或MT小鼠。MT和KO小鼠在乙醇给药后均表现出较低的乙醇偏好和较短的恢复时间。与WT小鼠相比，Usp 46 MT和KO小鼠在蔗糖偏好试验、新奇性抑制摄食试验和大理石埋藏试验中分别表现出降低的蔗糖偏好、更长的咬小球潜伏期和更多的埋藏大理石。在新物体识别测试中，MT和KO小鼠在训练后24小时都没有表现出对新物体的探索增加。这些发现表明，USP 46调节可能与人类精神障碍相关的广泛行为表型，并提供了对USP 46去泛素化酶在神经系统中功能的深入了解。
We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST) and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92), and mice with this mutation (MT mice), as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA) receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT) or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system.
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影响因子：
3.7
作者：
Imai S;Mamiya T;Tsukada A;Sakai Y;Mouri A;Nabeshima T;Ebihara S
通讯作者：
Ebihara S
影响因子：
8.2
作者：
Choleris, E;Thomas, AW;Prato, FS
通讯作者：
Prato, FS
影响因子：
3.4
作者：
Egashira, Nobuaki;Abe, Moe;Fujiwara, Michihiro
通讯作者：
Fujiwara, Michihiro
影响因子：
4.2
作者：
Cai, You-Qing;Cai, Guo-Qiang;Fei, Jian
通讯作者：
Fei, Jian
DOI：
10.1111/j.1530-0277.2001.tb02179.x
发表时间：
2001-12-01
影响因子：
3.2
作者：
Mihalek, RM;Bowers, BJ;Homanics, GE
通讯作者：
Homanics, GE