Study on molecular basis of behavior by transgenic technique

为了了解行为的分子基础，我们计划系统地培养过表达或缺乏特定神经肽或其受体的转基因小鼠。这些研究是与密歇根大学的Linda C.Samuelson博士和Sally A.Camper博士合作进行的。我们重点研究了几种神经肽，如神经肽Y （NPY）、胆囊收缩素（CCK）、胰腺多肽（PP）和促肾上腺皮质激素释放因子（CRF），它们都被报道在喂养、情绪和学习行为中起重要作用。NPY是哺乳动物大脑中最丰富的肽递质之一，被认为在行为及其疾病中发挥重要作用。为了了解NPY对神经元功能的长期调节作用，我们用与小鼠NPY cDNA连接的人类Thy-1基因片段的新型神经元特异性表达载体构建了转基因小鼠。转基因小鼠表现出焦虑、空间工作记忆中度缺陷和肾上腺束状带细胞肥大等行为特征，但未观察到其他行为缺陷。这些结果表明，大脑NPY在焦虑行为中起作用，这种遗传模型为研究人类焦虑和情绪障碍提供了独特的机会。我们没有尝试开发其他新的转基因模型来理解和治疗人类行为及其失调。不幸的是，1995年1月17日发生的里氏7.2级的神户地震，使我们位于神户地区的拥有现代医疗设施和技术的医院遭受了严重的结构性和非结构性破坏。这导致了我们项目的严重延误。

In order to understand the molecular basis of behavior, we planned to raise transgenic mice systemically that overxpress or lack the particullar neuropeptide or its receptor. These studies were performed in collaboration with Dr. Linda C.Samuelson and Dr. Sally A.Camper of Michigan University. We focused on several neuropeptides such as neuropeptide Y (NPY), cholecystokinin (CCK), pancreatic polypetide (PP), and corticotropin-releasing factor (CRF), all of which were reported to have important roles on feeding, emotion, and learning behaviors.NPY, one of the most abundant peptide transmitters in the mammalianbrain is assumed to play an important role in behavior and its disorders. To understand the long-term modulation of neuronal functions by NPY, we raised transgenic mice created with a novel neuron-specific expression vector of human Thy-1 gene fragment linked to mouse NPY cDNA.The transgenic mice displayd behavioral signs of anxiety, a moderate defect in spatial working memory, and hypertrophy of adrenal zona fasciculata cells, but no other behavioral defects were observed. These results suggest that brain NPY has a role in the anxiogenic behavior and that this genetic model provides an unique opportunity to study human anxiety and emotional disorders.We are non trying to develop other novel transgenic models for understanding and treatment of human behavior and its disorders. Unfortunately, by the Kobe earthquake occurred on 17 January 1995 with a magnitude of 7.2 on the Richter scale, our hospitals equipped with modern medical facilities and technologies situated in the Kobe area sufferd severe structural as well as non-structural damage.This resulted in considerable delay in our project.