Odor preference and olfactory memory are impaired in Olfaxin-deficient
Odor preference and olfactory memory are impaired in Olfaxin-deficient
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缺乏 Olfaxin 的人的气味偏好和嗅觉记忆受损
DOI：
10.1016/j.brainres.2018.03.025
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发表时间：
2018
期刊：
影响因子：
2.9
通讯作者：
Nakagawa T.
中科院分区：
文献类型：
--
作者：
Islam S;Ueda M;Nishida E;Wang MX;Osawa M;Lee D;Itoh M;Nakagawa K;Tana;Nakagawa T.
Olfaxin是一种含有BNIP2和Cdc42GAP同源（BCH）结构域的蛋白，主要表达于嗅球（OB）的二尖瓣和簇状（M/T）细胞中。Olfaxin和Caytaxin在谷氨酸末端定位、肾型谷氨酰胺酶（KGA）相互作用和caspase-3底物方面相似，氨基酸同源性为56.3%。虽然Caytaxin蛋白的缺失导致了人类Cayman共济失调和突变小鼠的共济失调，但Olfaxin的功能在很大程度上是未知的。在这项研究中，我们使用CRISPR/Cas9系统产生了prune2gene突变小鼠（Prune2Ex16−/−；敲除[KO]小鼠），在此过程中，含有olfaxinmrna起始密码子的外显子16被删除。外显子16有80个核苷酸，包含在5个PRUNE2亚型中的4个，包括PRUNE2、BMCC1、BNIPXL和Olfaxin/BMCC1s。小鼠OB和梨状皮质中Olfaxin mrna和Olfaxin蛋白水平显著降低。尽管prune2mrna在脊髓中也明显减少，但脊髓和背根神经节（DRG）的大体解剖结构完好无损。此外，在KO小鼠中未观察到感觉和运动系统的紊乱。因此，在当前的研究中，我们研究了Olfaxin在PRUNE2、BMCC1和BNIPXL几乎不表达的嗅觉系统中的作用。在使用异性尿液气味和非社会性气味刺激（杏仁）时，KO小鼠的气味偏好受损。气味厌恶测试结果表明，KO小鼠的气味联想学习被破坏。此外，在KO小鼠梨状皮质中未观察到NMDAR2A/NMDAR2B亚基的转换。这些结果表明，Olfaxin可能在气味偏好和嗅觉记忆中起关键作用。
Olfaxin, which is a BNIP2 and Cdc42GAP homology (BCH) domain-containing protein, is predominantly expressed in mitral and tufted (M/T) cells in the olfactory bulb (OB). Olfaxin and Caytaxin, which share 56.3% amino acid identity, are similar in their glutamatergic terminal localization, kidney-type glutaminase (KGA) interaction, and caspase-3 substrate. Although the deletion of Caytaxin protein causes human Cayman ataxia and ataxia in the mutant mouse, the function of Olfaxin is largely unknown. In this study, we generatedPrune2gene mutant mice (Prune2Ex16−/−; knock out [KO] mice) using the CRISPR/Cas9 system, during which the exon 16 containing start codon ofOlfaxinmRNA was deleted. Exon 16 has 80 nucleotides and is contained in four of fivePrune2isoforms, including PRUNE2, BMCC1, BNIPXL, and Olfaxin/BMCC1s. The levels ofOlfaxinmRNA and Olfaxin protein in the OB and piriform cortex ofKOmice significantly decreased. AlthoughPrune2mRNA also significantly decreased in the spinal cord, the gross anatomy of the spinal cord and dorsal root ganglion (DRG) was intact. Further, disturbance of the sensory and motor system was not observed in KO mice. Therefore, in the current study, we examined the role of Olfaxin in the olfactory system where PRUNE2, BMCC1, and BNIPXL are scarcely expressed. Odor preference was impaired in KO mice using opposite-sex urinary scents as well as a non-social odor stimulus (almond). Results of the odor-aversion test demonstrated that odor-associative learning was disrupted in KO mice. Moreover, the NMDAR2A/NMDAR2B subunits switch in the piriform cortex was not observed in KO mice. These results indicated that Olfaxin may play a critical role in odor preference and olfactory memory.