Loss of the SV2-like protein SVOP produces no apparent deficits in laboratory mice.

Loss of the SV2-like protein SVOP produces no apparent deficits in laboratory mice.
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DOI:
10.1371/journal.pone.0068215
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Bajjalieh SM
Bajjalieh SM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yao J;de la Iglesia HO;Bajjalieh SM

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神经元表达两个家族的转运蛋白−突触囊泡蛋白2(SV2A、B和C)以及SV2相关蛋白(SVOP和SVOPL)。这两个家族在结构上都与主要促进者(MF)转运蛋白家族相似。SV2存在于所有神经元和内分泌细胞中,与其在调节胞吐中发挥关键作用一致。与SV2一样,SVOP在所有脑区都有表达,其中小脑、后脑和松果体的表达水平最高。此外,SVOP在发育过程中的表达早于SV2,是衰老过程中表达下降幅度最大的神经元蛋白之一。虽然SV2对于生存是必不可少的,但它不是发育所必需的。因为在缺乏SV2的情况下,神经传递的显著水平仍然存在,所以有人提出,SVOP执行与SV2相似的功能,减轻SV2基因敲除小鼠的表型。为了测试这一点,我们产生了SVOP基因敲除小鼠和SVOP/SV2A/SV2B三重基因敲除小鼠。缺乏SVOP的小鼠是存活的、可生育的和表型正常的。对依赖小脑和松果体的神经传递和行为的测量显示,没有可测量的表型。SVOP/SV2A/SV2B三重基因敲除小鼠没有表现出比SV2A/SV2B基因缺失小鼠更严重的表型。这些发现支持这样一种解释,即SVOP执行一种独特的、虽然微妙的功能,但在正常情况下并不是生存所必需的。
Neurons express two families of transporter-like proteins − Synaptic Vesicle protein 2 (SV2A, B, and C) and SV2-related proteins (SVOP and SVOPL). Both families share structural similarity with the Major Facilitator (MF) family of transporters. SV2 is present in all neurons and endocrine cells, consistent with it playing a key role in regulated exocytosis. Like SV2, SVOP is expressed in all brain regions, with highest levels in cerebellum, hindbrain and pineal gland. Furthermore, SVOP is expressed earlier in development than SV2 and is one of the neuronal proteins whose expression declines most during aging. Although SV2 is essential for survival, it is not required for development. Because significant levels of neurotransmission remain in the absence of SV2 it has been proposed that SVOP performs a function similar to that of SV2 that mitigates the phenotype of SV2 knockout mice. To test this, we generated SVOP knockout mice and SVOP/SV2A/SV2B triple knockout mice. Mice lacking SVOP are viable, fertile and phenotypically normal. Measures of neurotransmission and behaviors dependent on the cerebellum and pineal gland revealed no measurable phenotype. SVOP/SV2A/SV2B triple knockout mice did not display a phenotype more severe than mice harboring the SV2A/SV2B gene deletions. These findings support the interpretation that SVOP performs a unique, though subtle, function that is not necessary for survival under normal conditions.
DOI: 10.1159/000335994
发表时间: 2012
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影响因子: 4.1
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发表时间: 1996-05-14
影响因子: 11.1
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发表时间: 2007-11-01
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