Gngt1-KO Mouse

Gngt1, which encodes the rod photoreceptor transducin gamma-subunit, is a key component in the phototransduction cascade within rod photoreceptor cells of the retina [4,5,6,7]. As part of the heterotrimeric G-protein transducin, it contributes to the signal transduction and amplification in the visual system. The gene is evolutionarily conserved, with its family expanding during early vertebrate tetraploidizations, suggesting a role in visual specializations [6].

In lung adenocarcinoma (LUAD), Gngt1 has emerged as a significant factor. High expression of Gngt1 in LUAD patients is associated with poor prognosis, advanced lymph node metastasis, and altered immune cell infiltration. Through gene set enrichment and other analyses, it was found that Gngt1 is involved in processes like DNA replication and cell adhesion molecule regulation. In a transgenic mouse model overexpressing Gngt1 under a lung-specific promoter, Gngt1 promoted epithelial-mesenchymal transformation, remodeled the tumor microenvironment, and led to tumor metastasis, worsening the survival-related prognosis of LUAD patients [2]. Additionally, in a study on non-small-cell lung cancer (NSCLC), Gngt1 was identified as one of the hub genes, and high expression was significantly associated with worse overall survival. Logistic regression analysis indicated that combining Gngt1 with NMU improved the ability to discriminate NSCLC [3]. In the context of atrial fibrillation-related stroke, Gngt1 was identified as a hub-gene potentially associated with stroke [1].

In conclusion, Gngt1 plays a crucial role in phototransduction in the retina. Its overexpression in certain cancers, particularly LUAD and NSCLC, is linked to poor prognosis and metastasis. The use of transgenic mouse models has been instrumental in elucidating its role in tumor-related processes. Also, its association with atrial fibrillation-related stroke indicates its potential as a biomarker or therapeutic target in stroke. These findings highlight the importance of Gngt1 in both normal visual function and disease-related biological processes.

References:

1. Zou, Rongjun, Zhang, Dingwen, Lv, Lei, Yang, Songran, Hua, Ping. 2019. Bioinformatic gene analysis for potential biomarkers and therapeutic targets of atrial fibrillation-related stroke. In Journal of translational medicine, 17, 45. doi:10.1186/s12967-019-1790-x. https://pubmed.ncbi.nlm.nih.gov/30760287/

2. Fan, Lin-Lin, Wang, Xiao-Wei, Zhang, Xiu-Mei, Yu, Hong, Jiang, Geng-Xi. 2025. GNGT1 remodels the tumor microenvironment and promotes immune escape through enhancing tumor stemness and modulating the fibrinogen beta chain-neutrophil extracellular trap signaling axis in lung adenocarcinoma. In Translational lung cancer research, 14, 239-259. doi:10.21037/tlcr-2024-1200. https://pubmed.ncbi.nlm.nih.gov/39958208/

3. Zhang, Jia-Jia, Hong, Jiang, Ma, Yu-Shui, Fu, Da, Yu, Fei. 2021. Identified GNGT1 and NMU as Combined Diagnosis Biomarker of Non-Small-Cell Lung Cancer Utilizing Bioinformatics and Logistic Regression. In Disease markers, 2021, 6696198. doi:10.1155/2021/6696198. https://pubmed.ncbi.nlm.nih.gov/33505535/

4. Scherer, S W, Feinstein, D S, Oliveira, L, Tsui, L C, Pittler, S J. . Gene structure and chromosome localization to 7q21.3 of the human rod photoreceptor transducin gamma-subunit gene (GNGT1). In Genomics, 35, 241-3. doi:. https://pubmed.ncbi.nlm.nih.gov/8661128/

5. Kolesnikov, Alexander V, Lobysheva, Elena, Gnana-Prakasam, Jaya P, Kefalov, Vladimir J, Kisselev, Oleg G. 2022. Regulation of rod photoreceptor function by farnesylated G-protein γ-subunits. In PloS one, 17, e0272506. doi:10.1371/journal.pone.0272506. https://pubmed.ncbi.nlm.nih.gov/35939447/

6. Lagman, David, Sundström, Görel, Ocampo Daza, Daniel, Abalo, Xesús M, Larhammar, Dan. 2012. Expansion of transducin subunit gene families in early vertebrate tetraploidizations. In Genomics, 100, 203-11. doi:10.1016/j.ygeno.2012.07.005. https://pubmed.ncbi.nlm.nih.gov/22814267/

7. Chen, Hui, Leung, Tinchung, Giger, Kathryn E, Hansen, Carl A, Robishaw, Janet D. 2007. Expression of the G protein gammaT1 subunit during zebrafish development. In Gene expression patterns : GEP, 7, 574-83. doi:. https://pubmed.ncbi.nlm.nih.gov/17306630/