WD repeat domain 3 遺伝子ヘテロ欠損マウス海馬におけるNMDA受容体 (NR2A, NR2B) の発現低下

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  • 小林 桃子
    国立精神・神経医療研究セ・精神保健研究所・精神薬理研究部
  • 古家 宏樹
    国立精神・神経医療研究セ・精神保健研究所・精神薬理研究部
  • 三輪 秀樹
    国立精神・神経医療研究セ・精神保健研究所・精神薬理研究部
  • 山田 美佐
    国立精神・神経医療研究セ・精神保健研究所・精神薬理研究部
  • 山田 光彦
    国立精神・神経医療研究セ・精神保健研究所・精神薬理研究部

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  • Reduced expression of NMDA receptors (NR2A and NR2B) in the hippocampus of WD repeat domain 3 gene hetero knockout mice

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<p>We have previously reported that both methamphetamine (an indirect dopamine agonist) and phencyclidine (an antagonist of the NMDA receptor) enhanced mRNA expression of WD repeat domain 3 (WDR3) gene in the rat brain. However, the physiological function of WDR3 in the brain is still unclear. </p><p>In the present study, we developed a novel polyclonal antibody to identify mouse WDR3 protein, and tested their specificity by antibody absorption tests and western blot analysis. Then, we examined the WDR3 expression in the brain of C57BL/6N mouse using immunohistochemistry. In addition, we performed X-gal staining using brain slices obtained from WDR3 hetero knockout (WDR3-HKO) mice, which had been produced using cryopreserved sperm of WDR3-flox mice by our group. As a result, a high expression of WDR3 was observed in the hippocampal CA1 region, although WDR3 was widely expressed in the central nervous system. Interestingly, mRNA expression of NR2A and NR2B-containing NMDA receptors were significantly decreased in the hippocampus of WDR3-HKO mice compared with wild-type mice (P= 0.0262 and 0.0063, respectively). </p><p>These results may suggest that WDR3 presumably associate with the hippocampus dependent cognitive function. Behavioral experiments to evaluate the hippocampus dependent cognitive function are warranted in our future studies.</p>

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