NISHIZAKI Tomoyuki Kobe University, Hyogo College of Medicine, Professor, 医学部, 教授 (00221474)
MATSUMOTO Akira Kobe University, Graduate School of Medicine, Associate Professor, 医学系研究科・医学部, 助教授 (80181759)
|Budget Amount *help
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥3,400,000 (Direct Cost: ¥3,400,000)
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.
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
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