Gabrq-KO Mouse

GABRQ, encoding the gamma-aminobutyric acid (GABA) A receptor subunit theta, is a crucial component of the GABAA receptor. GABA is the main inhibitory neurotransmitter in the brain, and the GABAA receptor, composed of subunits like GABRA3, GABRB3, and GABRQ, plays a key role in regulating neuronal excitability, thus being important for normal brain function and related biological processes [1].

GABRQ has been associated with multiple diseases. In clear cell renal cell carcinoma (ccRCC), low GABRQ mRNA expression was significantly linked to a poor prognosis, suggesting it could be a novel prognostic biomarker [1]. In hepatocellular carcinoma, GABRQ was overexpressed in cell lines and some tissues, and knockdown of endogenous GABRQ in HepG2 cells attenuated cell growth, indicating its role in promoting cancer cell viability [5]. In frontotemporal dementia (FTD), the loss of GABRQ-expressing von Economo neurons (VENs) and pyramidal neurons was associated with TDP43 and FUS pathology, and the severity of early behavioral symptoms correlated with a lower count of these neurons [2,6]. A missense coding variant rs3810651 in GABRQ was studied in Autism Spectrum Disorder (ASD), with a marginally higher frequency of "A" allele and "AA" genotype in female probands, who also showed higher severity in certain aspects [3]. Additionally, GABRQ rs3810651 might play a role in modifying the age at onset of migraine [4].

In conclusion, GABRQ is essential for the function of the GABAA receptor and neuronal excitability regulation. Its role in various diseases, such as ccRCC, hepatocellular carcinoma, FTD, ASD, and migraine, has been demonstrated through different studies. Understanding GABRQ could provide insights into the pathogenesis of these diseases and potentially lead to new diagnostic and therapeutic strategies.

References:

1. Lee, Dongjun, Ha, Mihyang, Hong, Chae Mi, Oh, Sae-Ock, Kim, Yun Hak. 2019. GABRQ expression is a potential prognostic marker for patients with clear cell renal cell carcinoma. In Oncology letters, 18, 5731-5738. doi:10.3892/ol.2019.10960. https://pubmed.ncbi.nlm.nih.gov/31788046/

2. Gami-Patel, Priya, Scarioni, Marta, Bouwman, Femke H, Hoozemans, Jeroen J M, Dijkstra, Anke A. 2022. The severity of behavioural symptoms in FTD is linked to the loss of GABRQ-expressing VENs and pyramidal neurons. In Neuropathology and applied neurobiology, 48, e12798. doi:10.1111/nan.12798. https://pubmed.ncbi.nlm.nih.gov/35152451/

3. Saha, Sharmistha, Chatterjee, Mahasweta, Sinha, Swagata, Mukhopadhyay, Kanchan. 2021. A pioneering study indicate role of GABRQ rs3810651 in ASD severity of Indo-Caucasoid female probands. In Scientific reports, 11, 7010. doi:10.1038/s41598-021-86496-5. https://pubmed.ncbi.nlm.nih.gov/33772085/

4. García-Martín, Elena, Esguevillas, Gara, Serrador, Mercedes, Agúndez, José A G, Jiménez-Jiménez, Félix Javier. 2018. Gamma-aminobutyric acid (GABA) receptors GABRA4, GABRE, and GABRQ gene polymorphisms and risk for migraine. In Journal of neural transmission (Vienna, Austria : 1996), 125, 689-698. doi:10.1007/s00702-017-1834-4. https://pubmed.ncbi.nlm.nih.gov/29299688/

5. Li, Yue-Hui, Liu, Yan, Li, Yan-Dong, Xie, Ping-Li, Li, Guan-Cheng. . GABA stimulates human hepatocellular carcinoma growth through overexpressed GABAA receptor theta subunit. In World journal of gastroenterology, 18, 2704-11. doi:10.3748/wjg.v18.i21.2704. https://pubmed.ncbi.nlm.nih.gov/22690081/

6. Gami-Patel, P, van Dijken, I, van Swieten, J C, Hoozemans, J J M, Dijkstra, A A. 2019. Von Economo neurons are part of a larger neuronal population that are selectively vulnerable in C9orf72 frontotemporal dementia. In Neuropathology and applied neurobiology, 45, 671-680. doi:10.1111/nan.12558. https://pubmed.ncbi.nlm.nih.gov/31066065/