GABA transporter mGat4 is involved in multiple neural functions in mice

• Published in: Biochimica et biophysica acta. Molecular cell research Vol. 1871; no. 5; p. 119740
• Main Authors: Ying, Yue, Liu, Weitong, Wang, Haoyue, Shi, Jiahao, Wang, Zhugang, Fei, Jian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2024
• Subjects: Behavioral analyses; GABA transporter; mGat4; Neurological disorders; Behavioral analyses; GABA transporter; mGat4; Neurological disorders
• ISSN: 0167-4889; 1879-2596
• DOI: 10.1016/j.bbamcr.2024.119740

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, GABAA 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. •mGat4-deficient mice showed impaired motor coordination and balance.•mGat4 deletion had a palliative effect on nociception.•mGat4 deficiency led to anti-anxiety-like and anti-depressive-like behavior and impaired learning and memory.•Multiple GABA-related molecules were altered in the brain of mGat4−/− mice.