Ask about this productRelated genes to: GABRG3 Blocking Peptide
- Gene:
- GABRG3 NIH gene
- Name:
- gamma-aminobutyric acid type A receptor gamma3 subunit
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 15q12
- Locus Type:
- gene with protein product
- Date approved:
- 1994-07-15
- Date modifiied:
- 2016-02-04
Related products to: GABRG3 Blocking Peptide
Related articles to: GABRG3 Blocking Peptide
- Sleep disorders are a core feature of Angelman syndrome (AS), affecting approximately 80% of individuals. They typically manifest as insomnia and disrupted sleep-wake cycles and contribute substantially to the burden experienced by affected individuals and their families. AS is caused by loss of function of the ubiquitin protein ligase E3A (UBE3A) gene, which encodes the E3 ubiquitin ligase E6AP, a protein essential for synaptic development and function. In individuals with a maternal 15q11-q13 deletion, concomitant deletion of neighboring non-imprinted genes, including GABRB3, GABRA5, GABRG3, ATP10A, and HERC2, may also contribute to the phenotype. Evidence from animal models further indicates that UBE3A plays a key role in sleep homeostasis and circadian rhythm regulation, including through interactions with core clock genes such as BMAL1. In this narrative review, we examine the role of UBE3A in sleep regulation and outline the principal sleep disturbances observed in AS, integrating findings from both preclinical models and human studies, while also considering genotype-phenotype correlations for the main clinical manifestations. The available evidence suggests that sleep disruption may be closely linked to the core neurological and behavioral features of AS, particularly epilepsy and behavioral abnormalities, through shared pathophysiological mechanisms related to UBE3A deficiency. Early identification and management of sleep disturbances may therefore represent a potentially modifiable factor for improving behavioral outcomes, seizure control, and overall quality of life in individuals with AS. In addition, sleep measures should be considered as potentially relevant clinical endpoints in ongoing trials of emerging therapeutic strategies. - Source: PubMed
Publication date: 2026/08/14
Terrone GaetanoMiano Maria GiuseppinaCarotenuto MarcoFiorile Maria FrancescaAiello SalvatoreBravaccio CarmelaDel Giudice Ennio - Brain-derived neurotrophic factor (BDNF) is a master regulator of neuronal differentiation and inhibitory circuit maturation in the mammalian brain. Yet, its downstream mediators in distinct neuronal populations remain incompletely defined. Here, we identify mitogen- and stress-activated kinase 1 (MSK1) as a critical mediator of BDNF signalling during postnatal striatal development. MSK1 expression predominates in GABAergic neurons across the cortex and striatum, with region-specific dynamics: MSK1 expression in cortical GABAergic interneurons declines from postnatal day 5 (P5) to day 30 (P30), while expression in striatal GABAergic medium spiny neurons (MSNs) persists into adulthood. Using a novel Msk1 KO mouse model, generated by deleting exon IV of Msk1, we find that striatal volume and MSN dendritic complexity decrease by P60, without cortical neuron alterations, underscoring MSK1´s striatal-specific role. Mechanistically, MSK1 drives BDNF-induced MeCP2 phosphorylation at serine 421 in MSNs via MAPK/ERK, independently of CaMKII, forming a nuclear complex with MeCP2, thus amplifying MSK1´s role in transcriptional regulation. This MSK1-MeCP2 signalling is also involved in BDNF-dependent and independent morphological developmental processes of cultured striatal neurons. Accordingly, Msk1 KO striatum shows dysregulated GABAergic (Gad1, Gabrg3) and dopaminergic (Drd1, Drd2, Drd3) gene expression, mirroring profiles in MeCP2 deficient models. Behaviourally, Msk1 KO mice display hypersociability, impaired nest-building, and increased depressive-like behaviour in the forced swimming test, contributing to striatal circuit dysfunction. These findings link MSK1-mediated molecular disruptions to inhibitory circuit imbalances and behaviours reminiscent of psychiatric disorders, positioning MSK1 as a potential therapeutic target for neurodevelopmental and psychiatric disorders, including those associated with MeCP2 dysfunction. - Source: PubMed
Publication date: 2026/05/18
Varela-Andrés NataliaHernández-Del Caño CarlosCebrián-León AlejandroBlanco AdriánLos Arcos-López de Pariza IzaskunFernández Del Campo Inés SGarcía-Losada SandraArévalo Juan CarlosSánchez-Martín ManuelBajo-Grañeras RaquelMartín RicardoSánchez-Aguilera AlbertoMerchán Miguel ADeogracias Rubén - has traditionally been used as a phytotherapeutic agent for cardiovascular, metabolic, immune, nervous, and reproductive health. In this study, a multidisciplinary approach combining nutrigenomic analyses, cardiovascular physiology experiments, and phytochemical and ethnobotanical data was employed to investigate the effects of aqueous extract (ZLex). ZLex significantly upregulated genes involved in nitric oxide synthesis (, ), smooth muscle relaxation, and angiotensin degradation, correlating with reductions in systolic, diastolic, and mean arterial blood pressure. In addition, ZLex modulated key neurotransmission-related genes (, , ), supporting its potential anxiolytic and neuroprotective actions. Immune modulation was indicated by the upregulation of genes associated with anti-inflammatory and antimicrobial responses. Metabolic benefits were linked to the regulation of genes involved in glucose and lipid metabolism, mitochondrial function, and body weight control. Positive effects on reproductive health were suggested by the induction of genes implicated in spermatogenesis. These effects are likely mediated by bioactive constituents such as rutin, kaempferol-3-O-rutinoside, 3',5'-di-C-β-glucopyranosylphloretin, a quercetin dirhamnosyl-galactoside, and myricetin-3-O-rutinoside. Altogether, the findings provide mechanistic support for the traditional use of and highlight its therapeutic potential in managing hypertension and other chronic disorders, including diabetes, obesity, and anxiety. - Source: PubMed
Publication date: 2026/03/04
Alla ChaimaeLucau-Danila AncaMehiou AfafAkissi Zachee L EHilbert Jean-LouisLegssyer AbdelkhaleqSahpaz SevserZiyyat Abderrahim - We investigated the correlation between increased gene copy number of gamma aminobutyric acid type A (GABA) receptor α5-containing subunits and electrophysiological and behavioral phenotypes in a mouse model of Dup15q syndrome (15q dup) and tested the hypothesis that selectively inhibiting the activity of GABA-α5 receptors may have therapeutic effects. Dup15q syndrome is a rare neurodevelopmental disorder caused by copy number gains of the 15q11.2-q13.1 chromosomal region, which includes UBE3A and a cluster of three genes (GABRA5, GABRB3, and GABRG3) encoding GABA receptor subunits, all of which are critical for neural development and function. Most affected children display hypotonia, motor delays, intellectual disability, and epilepsy, as well as a characteristic electroencephalography (EEG) beta-band phenotype. There is no disease-modifying therapy available. Autoradiography showed increased density of GABA-α5 receptors in the brains of 15q dup mice, while electrophysiology revealed enhanced GABAergic transmission in hippocampal slices from these mice. A GABA-α5 negative allosteric modulator, RO4938581, decreased inhibitory synaptic charge transfer in 15q dup hippocampal slices. The behavioral analyses confirmed inflexibility in learning and abnormal social behaviors in 15q dup mice, and both phenotypes were normalized following chronic treatment with RO4938581. EEG recordings showed increased beta-power in 15q dup mice - which resembled the spectral signature of subjects with Dup15q - and was partially normalized following RO4938581 treatment. Our results suggest that excessive expression and function of the GABA-α5 receptor subtype plays a key role in the pathophysiology of Dup15q and GABA-α5 NAMs may represent a potential precision medicine therapeutic option. - Source: PubMed
Publication date: 2026/01/05
Nakagawa RyokoNani FrancescaHipp Joerg FHoner MichaelKnoflach FredericGasser RodolfoOzmen LaurenceTamada KotaFjeldskaar FatihaTakacs LiviaVautheny AudreyMorairty Stephen RSaxe MichaelTakumi ToruHernandez Maria-Clemencia - Egg components, including weight of yolk, albumen, and eggshell, are economically important traits in poultry breeding and production, and we thus conducted a genome-wide association study (GWAS) for them. We used an F resource population of hens ( = 142) in different periods of laying, obtained by crossing breeds with contrasting phenotypes, and then genotyped them using the Illumina Chicken 60K iSelect BeadChip. Significant associations were found between 33 single nucleotide polymorphisms (SNPs) and yolk weight at 18-28 weeks of age (YW1). Eighty-seven SNPs were associated with thick albumen weight at 18-28 (TAW1) and 29-42 (TAW2) weeks of age. Four SNPs were associated with eggshell weight at 18-28 weeks of age (ESW1). Fifty-three candidate genes were identified in the positions of these SNPs, and seven prioritized candidate genes (PGCs) were revealed in regions where 2-4 SNPs associated with the studied traits were localized. These were as follows: (YW1, TAW1), (TAW1), (YW1, TAW1), (YW1), (YW1), (YW1), and (TAW1). Allelic variants at the , , , and loci were associated with higher YW1 and TAW1. These SNPs and PGCs are potential genetic markers for characterizing egg weight parameters and their components in chicken breeding to achieve egg production improvements. - Source: PubMed
Publication date: 2025/11/24
Volkova Natalia ARomanov Michael NLarionova Polina VDzhagaev Alan YuVolkova Ludmila ASermyagin Alexander AGriffin Darren KZinovieva Natalia A