Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, China.
PLoS One. 2011 Jan 5;6(1):e15998. doi: 10.1371/journal.pone.0015998.
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.
转录因子 Lmx1b 对于胚胎发育过程中中枢 5-羟色胺能（5-HTergic）神经元的分化和存活至关重要。然而，Lmx1b 在成年 5-HTergic 神经元中的作用尚不清楚。我们使用可诱导的 Cre-LoxP 系统选择性地使成年小鼠中缝核内的 Lmx1b 表达失活。生成了 Pet1-CreER(T2) 小鼠，并与 Lmx1b(flox/flox) 小鼠杂交，以获得 Pet1-CreER(T2); Lmx1b(flox/flox) 小鼠（称为 Lmx1b iCKO）。给予他莫昔芬后，Lmx1b iCKO 小鼠大脑中的 5-HT 水平降至对照小鼠的 60%，色氨酸羟化酶 2（Tph2）、血清素转运体（Sert）和囊泡单胺转运体 2（Vmat2）的表达也大大下调。另一方面，多巴胺和去甲肾上腺素以及芳香族 L-氨基酸脱羧酶（Aadc）和 Pet1 的表达不变。我们的结果表明，Lmx1b 是成年小鼠大脑中 5-HT 生物合成所必需的，它可能通过调节 Tph2、Sert 和 Vmat2 的表达来参与维持中枢 5-HTergic 神经元的正常功能。
