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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 .

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