Ying Yue, Liu Weitong, Wang Haoyue, Shi Jiahao, Wang Zhugang, Fei Jian
School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Shanghai Engineering Research Center for Model Organisms, SMOC, Shanghai 201203, China.
Biochim Biophys Acta Mol Cell Res. 2024 Jun;1871(5):119740. doi: 10.1016/j.bbamcr.2024.119740. Epub 2024 May 1.
γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. The termination of GABA transmission is through the action of GABA transporters (GATs). mGAT4 (encoded by Slc6a11) is another GAT besides GAT1 (encoded by Slc6a1) that functions in GABA reuptake in CNS. Research on the function of mGAT4 is still in its infancy. We developed an mGat4 knockout mouse model (mGat4 mice) and performed a series of behavioral analyses for the first time to study the effect of mGat4 on biological processes in CNS. Our results indicated that homozygous mGat4 mice had less depression, anxiety-like behavior and more social activities than their wild-type littermate controls. However, they had weight loss and showed motor incoordination and imbalance. Meanwhile, mGat4 mice showed increased pain threshold and hypoalgesia behavior in nociceptive stimulus and learning and memory impairments. The expression of multiple components of the GABAergic system including GAD67, GABA and KCC2 was altered. There is little or no compensatory change in mGat1. In a word, mGat4 may play a key role in normal motor coordination, sensation, emotion, learning and memory and could be the potential target of neurological disorders.
γ-氨基丁酸（GABA）是中枢神经系统中的主要抑制性神经递质。GABA传递的终止是通过GABA转运体（GATs）的作用实现的。mGAT4（由Slc6a11编码）是除GAT1（由Slc6a1编码）之外的另一种GAT，在中枢神经系统中发挥GABA再摄取的功能。对mGAT4功能的研究仍处于起步阶段。我们构建了一种mGat4基因敲除小鼠模型（mGat4小鼠），并首次进行了一系列行为分析，以研究mGat4对中枢神经系统生物学过程的影响。我们的结果表明，与野生型同窝对照小鼠相比，纯合子mGat4小鼠的抑郁和焦虑样行为较少，社交活动较多。然而，它们体重减轻，表现出运动不协调和失衡。同时，mGat4小鼠在伤害性刺激中表现出痛阈升高和痛觉减退行为，以及学习和记忆障碍。包括GAD67、GABA和KCC2在内的GABA能系统多个成分的表达发生了改变。mGat1几乎没有代偿性变化。总之，mGat4可能在正常的运动协调、感觉、情绪、学习和记忆中起关键作用，可能是神经疾病的潜在靶点。
