Roles of GABA in neural development and plasticity : produciton and analysis of GABA-synthesizing enzyme (GAD) -deficient mice

点击翻译按钮获取中文摘要

In order to elucidate the roles of gamma-aminobutyric acid (GABA) in the development of the neural and non-neural tissues and in the various functions of each brain region, the genes encoding GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD) in the mice were disrupted by gene targeting. GAD has two isoforms, GAD65 and GAD67, and expectedly their respective roles, so far unknown, would be clarified. GAD65-deficient mice could grow normally and did not show serious behavioral abnormailites. Their brain contained normal level of GABA and did not show histological abnormalities. On the other hand, GAD67-deficient mice were born as expected but died of severe cleft palate soon after birth. Their brain contained only 7% of GABA found in the wild-type brain in spite of their norman histoloy. These results have shown that GAD67 is an important isoform of GAD in the mouse brain. We are investigating on 1 involvement of GABA in development of palate and other non neural tissue and 2 production of GAD67-deficient mice rescued from cleft palate using inducible knockout technique. As GAD65 knockout mice showed moderate changes in responsiveness to convulsant and antipsychotic drugs, we are now analyzing the functions of the GAD65-deficient striatum, circadian system and other brain areas.