Study on the effect of endocrine disruptor on memory, learning and emotion in mice

为了研究内分泌干扰物对小鼠学习、记忆和情绪的影响，我们建立了敲除小鼠品系，该品系主要表达于小鼠大脑海马区。利用该系统对水迷宫系统中正常小鼠和基因敲除小鼠的LTP（Long-term potentiation）和海马依赖性记忆学习进行了研究。此外，我们还研究了羧基肽酶B在正常人和阿尔茨海默病患者海马亚区中的表达和分布。结果：1)与正常小鼠相比，Nell2基因敲除小鼠在水迷宫中表现出了正常的行为，正常小鼠和敲除小鼠都需要4 ~ 6次试验来学习水迷宫。另一方面，敲除小鼠对海马生理性LTP的诱导远高于正常小鼠，说明敲除小鼠的LTP系统变得更加敏感。2)在避免学习系统中，基因敲除小鼠比正常小鼠更快地学会避免电刺激。此外，基因敲除小鼠的记忆电刺激时间比正常小鼠长。这些结果表明，基因敲除小鼠可能在某些学习和记忆系统中增强，如避免学习。3)在对nel12基因敲除小鼠的研究中，我们发现nel12基因敲除小鼠存在雄性特异性受精缺陷。所有被敲除的雌蚊分别与+/+、-/+、-/-雄蚊交配怀孕。另一方面，所有基因敲除的雄性与+/+、-/+、-/-雌性受精均存在缺陷。这些结果清楚地表明，敲除nel12基因可诱导雄性特异性不受精。4)为了研究雄性特异性不受精的机制，我们研究了精子形成、精子运动、精子形态以及与精子-卵子结合相关的基因。敲除小鼠精子的活力、数量和形态均正常，说明敲除小鼠精子形成正常。5)我们还研究了正常小鼠和敲除小鼠中精卵结合因子（如受精素和胱氨酸）的基因表达。这两个基因在敲除小鼠的睾丸中表达正常。少

In order to study the effect of endocrine disrupter on learning, memory and emotion in mice, we have established knockout mouse strain defective to nel12 gene which is expressed mainly in hippocampus in mouse brain. Using this system, we have studied the LTP(Long-term potentiation) and hippocampal dependent memory and learning of normal, and knockout mice in water-maze system. Furthermore, we have studied expression and distribution of carboxypeptidase B in the subregions of the hippocampus of normal and Alzheimer's human brain.Result :1) Nell2 gene knockout mice has revealed normal behavior in water maze compared with normal mice : both normal and knockout mice require 4〜6 trials for learning water maze. On the other hand, the induction of physiological LTP in hippocampus was much higher in knockout mice than normal mice, indicating that LTP system in knockout mice become more sensitive.2) In avoiding learning system, knockout mice have learned to avoid electrical stimulation faster t … More han normal mice. Further, knockout mice have the electrical stimulation in memory longer than normal mice. These results indicate that knockout mice may be potentiated in certain leaning and memory system such as avoiding learning.3) During the study of nel12 gene knockout mice , we have found that the nel12 gene knockout mice are male-specifically defective in fertilization. All knockout female were pregnant in mating with +/+,-/+, -/- male, respectively. On the other hand, all knockout male were defective in fertilization with +/+,-/+, -/- female. These results clearly indicate that knockout of nel12 gene induces male-specific unfertilization.4) In order to study the mechanism of male-specific unfertilization, we have stdudied sperm formation, sperm motility, sperm morphology, and genes related to sperm-egg binding. Sperm in knockout mice was normal in its motility, number and morphology, indicating that sperm formation is normal in knockout mice.5) We have also studied gene expression of sperm-egg binding factors such as fertilin and cyritestin in normal and knockout mice. Both genes were expressed normally in knockout mice testis. Less