Abhd12-KO Mouse

Abhd12, an alpha/beta-hydrolase domain-containing serine hydrolase, is involved in regulating immunological and neurological mechanisms. It hydrolyzes endocannabinoid lipid transmitters and oxidized phosphatidylserine, and is part of the endocannabinoid system, playing a role in lipid signaling [2,5,6,7].

Knockdown of Abhd12 in breast cancer cells (MCF7 and MDA-MB-231) inhibits cell growth, proliferation, migration, and invasion, indicating its oncogenic role in breast cancer [1]. In hepatocellular carcinoma, knockout of Abhd12 sensitizes liver cancer cells to sorafenib-induced ferroptosis, as Abhd12 is upregulated in the cancer tissue, correlating with worse survival and contributing to tumorigenesis and sorafenib resistance [3]. In a mouse model, genetic deletion of Abhd12 leads to higher levels of lyso-PS lipids in the central nervous system and rapid rewiring of PS content, and concurrent deletion of LPCAT3 exacerbates auditory dysfunction and brain microgliosis, revealing their coordinated regulation of lipid content in the CNS [4].

In conclusion, Abhd12 is crucial in multiple biological processes. Its knockout or knockdown models have revealed its significant roles in cancer development and neurological diseases. In cancer, it promotes tumor growth and drug resistance, while in the nervous system, it is involved in lipid metabolism and related neuropathologies. These findings from model-based research provide insights into potential therapeutic targets for cancer and neurological disorders related to Abhd12 dysregulation.

References:

1. Jun, Semo, Kim, Seok Won, Lim, Ji-Yeon, Park, Seon-Joo. . ABHD12 Knockdown Suppresses Breast Cancer Cell Proliferation, Migration and Invasion. In Anticancer research, 40, 2601-2611. doi:10.21873/anticanres.14231. https://pubmed.ncbi.nlm.nih.gov/32366405/

2. Li, Taoxi, Feng, Yong, Liu, Yalan, Liu, Xuezhong, Ling, Jie. 2019. A novel ABHD12 nonsense variant in Usher syndrome type 3 family with genotype-phenotype spectrum review. In Gene, 704, 113-120. doi:10.1016/j.gene.2019.04.008. https://pubmed.ncbi.nlm.nih.gov/30974196/

3. Cai, Mengxing, Luo, Jingwen, Yang, Chunxiu, Ma, Lixin, Cheng, Yibin. 2023. ABHD12 contributes to tumorigenesis and sorafenib resistance by preventing ferroptosis in hepatocellular carcinoma. In iScience, 26, 108340. doi:10.1016/j.isci.2023.108340. https://pubmed.ncbi.nlm.nih.gov/38053637/

4. Ichu, Taka-Aki, Reed, Alex, Ogasawara, Daisuke, Tontonoz, Peter, Cravatt, Benjamin F. 2020. ABHD12 and LPCAT3 Interplay Regulates a Lyso-phosphatidylserine-C20:4 Phosphatidylserine Lipid Network Implicated in Neurological Disease. In Biochemistry, 59, 1793-1799. doi:10.1021/acs.biochem.0c00292. https://pubmed.ncbi.nlm.nih.gov/32364701/

5. Kelkar, Dhanashree S, Ravikumar, Govindan, Mehendale, Neelay, Chakrapani, Harinath, Kamat, Siddhesh S. 2019. A chemical-genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase. In Nature chemical biology, 15, 169-178. doi:10.1038/s41589-018-0195-0. https://pubmed.ncbi.nlm.nih.gov/30643283/

6. Kind, Laura, Kursula, Petri. 2018. Structural properties and role of the endocannabinoid lipases ABHD6 and ABHD12 in lipid signalling and disease. In Amino acids, 51, 151-174. doi:10.1007/s00726-018-2682-8. https://pubmed.ncbi.nlm.nih.gov/30564946/

7. Savinainen, J R, Saario, S M, Laitinen, J T. 2011. The serine hydrolases MAGL, ABHD6 and ABHD12 as guardians of 2-arachidonoylglycerol signalling through cannabinoid receptors. In Acta physiologica (Oxford, England), 204, 267-76. doi:10.1111/j.1748-1716.2011.02280.x. https://pubmed.ncbi.nlm.nih.gov/21418147/