The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia
The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia
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DOI：
10.1038/sj.mp.4000848
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发表时间：
2001-05-01
影响因子：
11
通讯作者：
Porteous, DJ
中科院分区：
文献类型：
--
作者：
Devon, RS;Anderson, S;Porteous, DJ
G蛋白偶联的代谢型谷氨酸受体（GRM/mGluRs）与精神分裂症的病因有关，因为它们调节NMDA反应以及其他神经递质（包括多巴胺和GABA）的反应。(1-3)在GRM亚型5敲除小鼠中的电生理学研究揭示，在一项研究中，精神分裂症的感觉运动门控缺陷特征（4），在另一项研究中，该基因在海马NMDA依赖性突触可塑性的调节中起关键作用。(5)在人类中，精神分裂症患者与对照组相比，GRM 5水平在某些锥体细胞神经元中增加。(6)最后，GRM 5已被定位到11 q14，邻近一个易位，在一个大的苏格兰家族F23（MLOD评分6.0）中与精神分裂症和相关精神病分离。（7，8）我们确定了GRM 5的内含子/外显子结构，并鉴定了一个新的基因内微卫星。一项病例对照关联研究发现，精神分裂症患者和对照组之间的等位基因频率分布存在显著差异（P = 0.04）。这表明GRM 5基因参与了该人群中的精神分裂症。
The G-protein coupled metabotropic glutamate receptors (GRMs/mGluRs) have been implicated in the aetiology of schizophrenia as they modulate the NMDA response and that of other neurotransmitters including dopamine and GABA.(1-3) Electrophysiological studies in GRM subtype 5 knockout mice reveal, in one study, a sensorimotor gating deficit characteristic of schizophrenia(4) and in another, a key role for this gene in the modulation of hippocampal NMDA-dependent synaptic plasticity.(5) In humans, GRM5 levels are increased in certain pyramidal cell neurons in schizophrenics vs controls.(6) Finally, GRM5 has been mapped to 11q14, neighbouring a translocation that segregates with schizophrenia and related psychoses in a large Scottish family, F23 (MLOD score 6.0).(7,8) We determined the intron/exon structure of GRM5 and identified a novel intragenic microsatellite. A case-control association study identified a significant difference in allele frequency distribution between schizophrenics and controls (P = 0.04). This is suggestive of involvement of the GRM5 gene in schizophrenia in this population.