title: Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities.
abstract: Rett syndrome (RTT) is characterized by specific motor, cognitive, and behavioral deficits. Because several of these abnormalities occur in other disease states associated with alterations in aminergic neurotransmitters, we investigated the contribution of such alterations to RTT pathogenesis. We found that both individuals with RTT and Mecp2-null mice have lower-than-normal levels of aminergic metabolites and content. Deleting Mecp2 from either TH-positive dopaminergic and noradrenergic neurons or PET1-positive serotonergic neurons in mice decreased corresponding neurotransmitter concentration and specific phenotypes, likely through MeCP2 regulation of rate-limiting enzymes involved in aminergic neurotransmitter production. These data support a cell-autonomous, MeCP2-dependent mechanism for the regulation of aminergic neurotransmitter synthesis contributing to unique behavioral phenotypes.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Rodney C
authors.initials: RC
authors.lastname: Samaco
authors.forename: Caleigh
authors.initials: C
authors.lastname: Mandel-Brehm
authors.forename: Hsiao-Tuan
authors.initials: HT
authors.lastname: Chao
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Ward
authors.forename: Sharyl L
authors.initials: SL
authors.lastname: Fyffe-Maricich
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Keith
authors.initials: K
authors.lastname: Hyland
authors.forename: Christina
authors.initials: C
authors.lastname: Thaller
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Maricich
authors.forename: Peter
authors.initials: P
authors.lastname: Humphreys
authors.forename: John J
authors.initials: JJ
authors.lastname: Greer
authors.forename: Alan
authors.initials: A
authors.lastname: Percy
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Glaze
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Neul
mesh_terms: D000588:Amines / Q000378:metabolism*; D000818:Animals; D006719:Homovanillic Acid / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D001523:Mental Disorders / Q000378:metabolism*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D010641:Phenotype; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000588:Amines; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D006897:Hydroxyindoleacetic Acid; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; D006719:Homovanillic Acid