Adgrb3-KO Mouse

Adgrb3, also known as BAI3, belongs to the family of adhesion G protein-coupled receptors. It is most highly expressed in the brain, where it plays a role in synaptogenesis and synapse maintenance. It may also be involved in regulating aspects of the central nervous system such as axon guidance, myelination, and synapse formation. Genome-wide association studies have implicated it in disorders like schizophrenia, epilepsy, and psychiatric disorders [1,2,3].

A mouse line with a 7-base pair deletion in Adgrb3 exon 10 was generated using CRISPR/Cas9 editing. Homozygous mutants lacked full-length ADGRB3 expression. These mutant mice showed reduced brain and body weights and deficits in social interaction, suggesting Adgrb3's role in these aspects [2]. Additionally, SNPs within Adgrb3 introns were associated with lower fecal egg counts in Katahdin sheep, indicating its potential role in host response to gastrointestinal nematodes [5]. In cancer, somatic mutations in Adgrb3 have been identified, and in advanced biliary duct cancer, its mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival. In extensive-stage small cell lung cancer, alterations in Adgrb3 were predictors of favorable survival in patients receiving first-line chemoimmunotherapy [4,6,7].

In conclusion, Adgrb3 is crucial for normal brain development and function, as demonstrated by gene-knockout mouse models. Its involvement in various disease conditions, such as psychiatric disorders, nematode resistance in sheep, and different cancers, has been revealed through these in vivo studies. These findings emphasize the importance of Adgrb3 in understanding the genetic mechanisms underlying these biological processes and diseases.

References:

1. Hamann, Jörg, Aust, Gabriela, Araç, Demet, Langenhan, Tobias, Schiöth, Helgi B. . International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. In Pharmacological reviews, 67, 338-67. doi:10.1124/pr.114.009647. https://pubmed.ncbi.nlm.nih.gov/25713288/

2. Shiu, Fu Hung, Wong, Jennifer C, Bhattacharya, Debanjan, Van Meir, Erwin G, Escayg, Andrew. 2023. Generation and initial characterization of mice lacking full-length BAI3 (ADGRB3) expression. In Basic & clinical pharmacology & toxicology, 133, 353-363. doi:10.1111/bcpt.13917. https://pubmed.ncbi.nlm.nih.gov/37337931/

3. Scuderi, Carmela, Saccuzzo, Lucia, Vinci, Mirella, Romano, Corrado, Fichera, Marco. 2019. Biallelic intragenic duplication in ADGRB3 (BAI3) gene associated with intellectual disability, cerebellar atrophy, and behavioral disorder. In European journal of human genetics : EJHG, 27, 594-602. doi:10.1038/s41431-018-0321-1. https://pubmed.ncbi.nlm.nih.gov/30659260/

4. Zhang, Yu, Luo, Jia, Liu, Zhe, Wang, Lei, Song, Xinqiang. . Identification of hub genes in colorectal cancer based on weighted gene co-expression network analysis and clinical data from The Cancer Genome Atlas. In Bioscience reports, 41, . doi:10.1042/BSR20211280. https://pubmed.ncbi.nlm.nih.gov/34308980/

5. Becker, Gabrielle M, Burke, Joan M, Lewis, Ronald M, Notter, David R, Murdoch, Brenda M. 2022. Variants Within Genes EDIL3 and ADGRB3 are Associated With Divergent Fecal Egg Counts in Katahdin Sheep at Weaning. In Frontiers in genetics, 13, 817319. doi:10.3389/fgene.2022.817319. https://pubmed.ncbi.nlm.nih.gov/35360858/

6. Lu, Yunxin, Jin, Yin, Liu, Furong, Chi, Peidong, Zhang, Dongsheng. 2024. Efficacy of durvalumab plus chemotherapy in advanced biliary duct cancer and biomarkers exploration. In Cancer immunology, immunotherapy : CII, 73, 220. doi:10.1007/s00262-024-03796-1. https://pubmed.ncbi.nlm.nih.gov/39235609/

7. Jiang, Yuxin, Xie, Jingyuan, Cheng, Qinpei, Lv, Tangfeng, Zhan, Ping. 2024. Comprehensive genomic and spatial immune infiltration analysis of survival outliers in extensive-stage small cell lung cancer receiving first-line chemoimmunotherapy. In International immunopharmacology, 141, 112901. doi:10.1016/j.intimp.2024.112901. https://pubmed.ncbi.nlm.nih.gov/39151386/