Seeman Philip, Ko Françoise, Jack Elaine, Greenstein Rachel, Dean Brian
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
Synapse. 2007 May;61(5):303-9. doi: 10.1002/syn.20368.
It is known that RGS9-2 gene knockout mice show supersensitivity to DA and have a marked elevation in the proportion of DA D2 receptors in the high-affinity state for DA (D2(High) receptors). As this is a similar profile to that observed in the CNS from subjects with schizophrenia, we examined whether postmortem CNS tissue from subjects with the disorder and brain striata from an animal model of psychosis or schizophrenia (the amphetamine-sensitized rat) had altered levels of RGS9-2. The mRNA for RGS9-2 in 29 control hippocampi was 0.185 +/- 0.015 fg per fg of beta-glucuronidase mRNA (average +/- SE), while that in 29 schizophrenia hippocampi was 0.145 +/- 0.015 fg per fg of beta-glucuronidase mRNA (average +/- SE), a reduction of 22%. Of the many receptor-regulating genes related to G proteins, and of 11 RGS genes, RGS9-2 was the most reduced in the amphetamine-sensitized rat striatum. The reduced levels of RGS9-2 expression in both an animal model of schizophrenia and a postmortem schizophrenia brain provide further evidence implicating RGS9-2 as a candidate gene in schizophrenia.
已知RGS9 - 2基因敲除小鼠对多巴胺（DA）表现出超敏反应，并且处于对DA高亲和力状态的DA D2受体（D2（高）受体）比例显著升高。由于这与精神分裂症患者中枢神经系统（CNS）中观察到的情况相似，我们研究了患有该疾病的患者的死后CNS组织以及精神病或精神分裂症动物模型（苯丙胺致敏大鼠）的脑纹状体中RGS9 - 2水平是否发生改变。29个对照海马体中RGS9 - 2的mRNA为每微克β - 葡萄糖醛酸酶mRNA 0.185±0.015飞克（平均值±标准误），而29个精神分裂症海马体中的为每微克β - 葡萄糖醛酸酶mRNA 0.145±0.015飞克（平均值±标准误），降低了22%。在与G蛋白相关的众多受体调节基因以及11个RGS基因中，RGS9 - 2在苯丙胺致敏大鼠纹状体中减少最多。精神分裂症动物模型和死后精神分裂症大脑中RGS9 - 2表达水平的降低提供了进一步证据，表明RGS9 - 2是精神分裂症的候选基因。
