Ciaranello R D, Boehme R E
Behav Genet. 1982 Feb;12(1):11-35. doi: 10.1007/BF01065738.
This report begins with a summary of the evidence for genetic involvement in certain major psychiatric syndromes. The relation of these disorders to deficits in central nervous system neurotransmitters is also summarized. These reviews serve as an introduction to our studies on the genetic regulation of neurotransmitters and their enzymes and receptors in inbred mice. The steady-state levels of the adrenal catecholamine biosynthetic enzymes are controlled genetically; not only is each enzyme regulated by a single locus, but also there is statistical evidence that the phenotypic expression of the entire pathway is regulated by a single gene. Studies on the biochemical mechanism of gene action suggest that genetic regulation is exerted on proteolysis of the enzymes, rather than their synthesis. In addition, we have examined the genetic control of dopamine receptors in inbred mice. Dopaminergic receptors in the nigrostriatal and mesolimbic pathways are under genetic control. Preliminary evidence suggests that the pathways are regulated by different genetic systems. If this early speculation proves true, it would have important clinical implications.
本报告首先总结了基因与某些主要精神综合征之间存在关联的证据。这些疾病与中枢神经系统神经递质缺陷之间的关系也进行了总结。这些综述是我们对近交系小鼠神经递质及其酶和受体的基因调控研究的引言。肾上腺儿茶酚胺生物合成酶的稳态水平受基因控制；不仅每种酶由单个基因座调控，而且有统计学证据表明整个途径的表型表达受单个基因调控。对基因作用生化机制的研究表明，基因调控作用于酶的蛋白水解，而非其合成。此外，我们研究了近交系小鼠中多巴胺受体的基因控制。黑质纹状体和中脑边缘通路中的多巴胺能受体受基因控制。初步证据表明，这些通路受不同的基因系统调控。如果这一早期推测被证明是正确的，将具有重要的临床意义。
