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Adult raphe-specific deletion of Lmx1b leads to central serotonin deficiency.

ABSTRACT: 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.

SUBMITTER: Song NN

PROVIDER: S-EPMC3016403 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Adult raphe-specific deletion of Lmx1b leads to central serotonin deficiency.

Song Ning-Ning NN Xiu Jian-Bo JB Huang Ying Y Chen Jia-Yin JY Zhang Lei L Gutknecht Lise L Lesch Klaus Peter KP Li He H Ding Yu-Qiang YQ

PloS one 20110105 1

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 admini ...[more]

PMID: 21246047

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Adult raphe-specific deletion of Lmx1b leads to central serotonin deficiency.

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Adult raphe-specific deletion of Lmx1b leads to central serotonin deficiency.

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