Impaired auditory-vestibular functions and behavioral abnormalities of Slitrk6-deficient mice.

Impaired auditory-vestibular functions and behavioral abnormalities of Slitrk6-deficient mice.
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DOI:
10.1371/journal.pone.0016497
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发表时间:
2011-01-26
期刊:
影响因子:
3.7
通讯作者:
Aruga J
Aruga J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Matsumoto Y;Katayama K;Okamoto T;Yamada K;Takashima N;Nagao S;Aruga J

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最近的一项研究表明,Slitrk 6是一种含有富含亮氨酸重复结构域的跨膜蛋白,在内耳神经回路的发育中具有关键作用。然而,目前尚不清楚Slitrk 6的缺失如何影响听觉和前庭功能。此外,Slitrk 6在中枢神经系统区域(包括背侧丘脑)中的作用尚未得到解决。为了理解Slitrk 6的生理作用,对Slitrk 6敲除(KO)小鼠进行系统的行为分析,包括听觉和前庭功能测试。与野生型小鼠相比,Slitrk 6-KO小鼠的听性脑干反应(ABR)表明中频范围(8-16 kHz)听力损失和第一ABR波的减少。听觉惊吓反应也减少了。前庭眼反射(VOR)测试显示垂直(头部运动诱导)VOR增益降低,水平VOR正常。在旷场测试中,自发活动减少;在中心区域的倾向增加,但仅在测试的前5分钟,表明对新环境的适应性反应改变。在洞板测试中也发现了改变的适应性反应,其中头部下沉行为增加和先进。除这些异常外,在情绪、焦虑、学习、空间记忆或恐惧记忆相关行为测试中未观察到明显异常。这些结果表明,Slitrk 6-KO小鼠可以作为遗传性感音神经性耳聋的模型。此外,Slitrk 6-KO小鼠对新环境的反应改变表明Slitrk 6在一些认知功能中的作用。
A recent study revealed that Slitrk6, a transmembrane protein containing a leucine-rich repeat domain, has a critical role in the development of the inner ear neural circuit. However, it is still unknown how the absence of Slitrk6 affects auditory and vestibular functions. In addition, the role of Slitrk6 in regions of the central nervous system, including the dorsal thalamus, has not been addressed. To understand the physiological role of Slitrk6, Slitrk6-knockout (KO) mice were subjected to systematic behavioral analyses including auditory and vestibular function tests. Compared to wild-type mice, the auditory brainstem response (ABR) of Slitrk6-KO mice indicated a mid-frequency range (8–16 kHz) hearing loss and reduction of the first ABR wave. The auditory startle response was also reduced. A vestibulo-ocular reflex (VOR) test showed decreased vertical (head movement–induced) VOR gains and normal horizontal VOR. In an open field test, locomotor activity was reduced; the tendency to be in the center region was increased, but only in the first 5 min of the test, indicating altered adaptive responses to a novel environment. Altered adaptive responses were also found in a hole-board test in which head-dip behavior was increased and advanced. Aside from these abnormalities, no clear abnormalities were noted in the mood, anxiety, learning, spatial memory, or fear memory–related behavioral tests. These results indicate that the Slitrk6-KO mouse can serve as a model of hereditary sensorineural deafness. Furthermore, the altered responses of Slitrk6-KO mice to the novel environment suggest a role of Slitrk6 in some cognitive functions.
DOI: 10.1097/01.mao.0000169780.84588.a5
发表时间: 2005-05-01
影响因子: 2.1
作者:
Noushi, F;Richardson, RT;O'Leary, S
通讯作者: O'Leary, S
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发表时间: 2006-06-01
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影响因子: 1.7
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发表时间: 2009-12-15
期刊: PLOS ONE
影响因子: 3.7
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