Adult raphe-specific deletion of Lmx1b leads to central serotonin deficiency.
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-CreER(T2) mice were generated and crossed with Lmx1b(flox/flox) mice to obtain Pet1-CreER(T2); Lmx1b(flox/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.
Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, China. songnn1982@gmail.com
Ning-Ning
NN
Song
Jian-Bo
JB
Xiu
Ying
Y
Huang
Jia-Yin
JY
Chen
Lei
L
Zhang
Lise
L
Gutknecht
Klaus Peter
KP
Lesch
He
H
Li
Yu-Qiang
YQ
Ding
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D009474:Neurons; D012701:Serotonin / Q000096:biosynthesis / Q000172:deficiency*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*; D014365:Tryptophan Hydroxylase / Q000235:genetics; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics
D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493453:Slc18a2 protein, mouse; C493231:Slc6a4 protein, mouse; D014157:Transcription Factors; D050493:Vesicular Monoamine Transport Proteins; D013629:Tamoxifen; D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase
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