Gabrb3, encoding the β3 -subunit of the γ -aminobutyric acid type A (GABA_A) receptor, is crucial for inhibitory function in the brain. GABA_A receptors play a key role in the balance between neuronal excitation and inhibition, with GABA being the major inhibitory neurotransmitter in the brain [2,4]. Genetic models, such as knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying Gabrb3's function.

In Gabrb3 -ablated mice, there is a developmental decrease in GABAergic synapses, increased local network synchrony, and enhanced functional connectivity of contralateral pyramidal neuron subtypes. This indicates Gabrb3 is required for the functional integration of pyramidal neuron subtypes in the somatosensory cortex and for the emergence of interhemispheric circuits for sensory processing [1]. In Gabrb3 endothelial cell-specific knockout (Gabrb3ECKO) mice, deletion of the β3 subunit from endothelial cells leads to abnormal blood flow, hypertension, and behavioral deficits, suggesting vascular Gabrb3 is important in both the brain and heart [3].

In conclusion, Gabrb3 is essential for inhibitory function in the brain, playing a role in the integration of neuronal circuits for sensory processing and in maintaining normal vascular and behavioral functions. Studies using Gabrb3 KO/CKO mouse models have revealed its significance in neurodevelopmental disorders, epilepsy, and cardiovascular-behavioral comorbidities, contributing to a better understanding of these disease mechanisms.

References:

1. Babij, Rachel, Ferrer, Camilo, Donatelle, Alexander, Liston, Conor, De Marco García, Natalia V. 2022. Gabrb3 is required for the functional integration of pyramidal neuron subtypes in the somatosensory cortex. In Neuron, 111, 256-274.e10. doi:10.1016/j.neuron.2022.10.037. https://pubmed.ncbi.nlm.nih.gov/36446382/

2. Maillard, Pierre-Yves, Baer, Sarah, Schaefer, Élise, De Saint Martin, Anne, Milh, Mathieu. 2022. Molecular and clinical descriptions of patients with GABAA receptor gene variants (GABRA1, GABRB2, GABRB3, GABRG2): A cohort study, review of literature, and genotype-phenotype correlation. In Epilepsia, 63, 2519-2533. doi:10.1111/epi.17336. https://pubmed.ncbi.nlm.nih.gov/35718920/

3. Agrud, Anass, Subburaju, Sivan, Goel, Pranay, Kloner, Robert A, Vasudevan, Anju. 2022. Gabrb3 endothelial cell-specific knockout mice display abnormal blood flow, hypertension, and behavioral dysfunction. In Scientific reports, 12, 4922. doi:10.1038/s41598-022-08806-9. https://pubmed.ncbi.nlm.nih.gov/35318369/

4. Feng, Yan, Wei, Zi-Han, Liu, Chao, Zhang, Chu-Chu, Deng, Yan-Chun. 2022. Genetic variations in GABA metabolism and epilepsy. In Seizure, 101, 22-29. doi:10.1016/j.seizure.2022.07.007. https://pubmed.ncbi.nlm.nih.gov/35850019/