Adult Raphe-Specific Deletion of Lmx1b Leads to Central Serotonin Deficiency

PLoS One

Ying Huang¹  Yu-Qiang Ding¹  Jia-Yin Chen¹  Lei Zhang¹  Ning-Ning Song¹  Jian-Bo Xiu¹  He Li²  Klaus Peter Lesch³  Lise Gutknecht³ 

[1] Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, China;Key Laboratory of Nervous System Diseases, Ministry of Education of China, Division of Histology and Embryology, Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Molecular and Clinical Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany

关键词: Neurons;    Neuronal differentiation;    Serotonin;    Immunostaining;    Mouse models;    Dopamine;    High performance liquid chromatography;    In situ hybridization;   

DOI  :  10.1371/journal.pone.0015998

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

The transcription factor Lmx1b is essential for the differentiation and survival of central serotonergic (5-HTergic) neurons during embryonic development. However, the role of Lmx1b in adult 5-HTergic neurons is unknown. We used an inducible Cre-LoxP system to selectively inactivate Lmx1b expression in the raphe nuclei of adult mice. Pet1-CreERT2 mice were generated and crossed with Lmx1bflox/flox mice to obtain Pet1-CreERT2; Lmx1bflox/flox mice (which termed as Lmx1b iCKO). After administration of tamoxifen, the level of 5-HT in the brain of Lmx1b iCKO mice was reduced to 60% of that in control mice, and the expression of tryptophan hydroxylase 2 (Tph2), serotonin transporter (Sert) and vesicular monoamine transporter 2 (Vmat2) was greatly down-regulated. On the other hand, the expression of dopamine and norepinephrine as well as aromatic L-amino acid decarboxylase (Aadc) and Pet1 was unchanged. Our results reveal that Lmx1b is required for the biosynthesis of 5-HT in adult mouse brain, and it may be involved in maintaining normal functions of central 5-HTergic neurons by regulating the expression of Tph2, Sert and Vmat2.

【 授权许可】

CC BY