MECP2 regulates transcription of genes involved in GABA signaling

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Homo sapiens
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MECP2 regulates expression of several genes involved in GABA (gamma-aminobutyric acid) signaling. Transcription of GAD1 (GAD67) and GAD2 (GAD65) genes is directly positively regulated by MECP2. GAD1 and GAD2 are components of the glutamic acid decarboxylase complex involved in production of the neurotransmitter GABA. Mice lacking Mecp2 from GABA-releasing neurons have decreased GABA levels and exhibit multiple Rett syndrome features (Chao et al. 2010).

Mecp2 deletion in mouse GABAergic parvalbumin-expressing (PV) cells, cortical interneurons playing a key role in visual experience-induced ocular dominance plasticity, does not result in Rett-like phenotype, other than defects in motor coordination and motor learning. While functions of the visual cortex are preserved in mice lacking Mecp2 in GABAergic PV cells, the visual input-induced spiking responses are decreased. Mecp2 loss impairs maturation of membrane functions of cortical GABAergic PV cells. Mecp2 may be needed for PV cell-mediated cortical GABA inhibition. Mecp2-deficient cortical PV cells show reduced mRNA levels of several genes involved in GABA signaling, such as Parvalbumin, Gad2, Calretinin, Gabra1 and Gabra2, as well as reduced levels of Glu3, a glutamate receptor subunit, and Kv3.1, a potassium channel (He et al. 2014).

Literature References
PubMed ID Title Journal Year
25297674 Conditional deletion of Mecp2 in parvalbumin-expressing GABAergic cells results in the absence of critical period plasticity

Chen, XJ, Li, YD, Zhang, XH, Shu, YS, He, LJ, Liu, N, Qiu, ZL, Cheng, TL

Nat Commun 2014
21068835 Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes

Neul, JL, Chahrour, M, Xue, M, Samaco, RC, Noebels, JL, Zoghbi, HY, Rubenstein, JL, Chen, H, Lu, HC, Yoo, J, Ekker, M, Heintz, N, Rosenmund, C, Gong, S, Chao, HT

Nature 2010
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