JBC：精神分裂症易感基因DTNBP1的病理机制

2014-09-05 伊文中国科学院遗传与发育生物学研究所

DTNBP1是精神分裂症主要的易感基因之一，它编码的dysbindin-1在人体中存在3种异构体dysbindin-1A、1B、1C。已有的研究表明，精神分裂症患者海马中的dysbindin-1B和1C表达量减少，但1A正常。中国科学院遗传与发育生物学研究所李巍研究组利用不同小鼠突变体，发现dysbindin-1C特异性表达在海马齿状回的门区一类谷氨酸能神经元，其缺乏后导致这类神经元数目减少，

DTNBP1是精神分裂症主要的易感基因之一，它编码的dysbindin-1在人体中存在3种异构体dysbindin-1A、1B、1C。已有的研究表明，精神分裂症患者海马中的dysbindin-1B和1C表达量减少，但1A正常。

中国科学院遗传与发育生物学研究所李巍研究组利用不同小鼠突变体，发现dysbindin-1C特异性表达在海马齿状回的门区一类谷氨酸能神经元，其缺乏后导致这类神经元数目减少，进而影响其投射的齿状回中一类GABA中间神经元的CREB信号通路的减弱，导致成体产生的新生神经元成熟障碍，影响其参与海马CA区的环路整合，从而导致认知行为的改变。这项研究解释了精神分裂症患者海马dysbindin-1C减少的临床意义，并支持成体神经发生障碍在精神分裂症发生中的重要作用。

该项研究已在线发表于美国生化与分子生物学会期刊The Journal of Biological Chemistry(doi:10.1074/jbc.M114.590927)，并被遴选为“Papers of the week”，列为该期刊每年刊登的6000多篇论文中的前2%重要论文。李巍研究组的博士生王浩为论文第一作者，该论文得到国家自然科学基金委重大研究计划培育项目、中科院重点部署项目等的资助。

　　野生型DBA小鼠dysbindin-1在海马齿状回门区的表达

　　Dysibindin-1A和1C都缺乏的sdy小鼠缺乏阳性信号

Dysbindin-1C正常但1A缺乏的mu小鼠在海马齿状回门区的表达

原始出处

Wang H1, Yuan Y1, Zhang Z1, Yan H1, Feng Y1, Li W2.Dysbindin-1C is required for the survival of hilar mossy cells and the maturation of adult newborn neurons in dentate gyrus.J Biol Chem. 2014 Aug 25

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2014-12-29 lily1616

#JBC#

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2014-10-19 paperyu

#病理机制#

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2014-09-07 passed water

#易感基因#

40 0
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2014-09-07 bnurmamat

#精神分裂#

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