NPAS3基因在精神分裂症中的研究进展

NPAS 3是一种主要存在于大脑中的转录因子,属于碱性螺旋-环-螺旋超家族。NPAS 3基因位于14号染色体(14q 13),在精神分裂症患者中发现,NPAS 3基因在染色体9与14间[t(9;14)(q 34;q 13)]具有平衡易位现象;NPAS 3基因敲除小鼠具有多动、步态有缺陷、前脉冲抑制功能减弱等行为活动,这与精神分裂症症状相类似;NPAS 3基因有可能通过FGF信号通路调节海马区的神经发生,神经发生在精神分裂症的发生发展中具有重要的作用;显性负效、单倍剂量不足效应、转录后调控等有可能是调节NPAS3蛋白表达水平的不同机制。

NPAS3 is a member of the basic helix-loop-helix family of transcription factors expressed in the brain. The gene is located at 14q13 and a reciprocal balanced translocation between chromosomes 9 and 14 was identified in schizophrenia. A number of behavioural abnormalities associated with schizophrenia were identified in Npas3-？ - mice including locomotor hyperactivity, subtle gait defects, impairment of prepulse inhibition of acoustic startle. Correlative evidence suggests that neurogenesis may play an important role in schizophrenia, NPAS3 gene may regulates the hippocampal neurogenesis through the FGF signal pathway. The transcription regulation mechanisms of NPAS3 protein expression level might be involved dominant negative, haploinsufficiency and posttranscriptional regulation.