Dagla-KO Mouse

DAGLA, or diacylglycerol lipase alpha, is an important hydrolytic enzyme that yields 2-AG and free fatty acids. It is involved in the endocannabinoid system, which modulates various biological processes [1,2,4]. The endocannabinoid system has broad-ranging effects and DAGLA-produced 2-AG is known to be involved in processes like axonal growth during brain development and retrograde synaptic signaling at mature synapses [5].

In gene-knockout (KO) mouse models, specific inducible deletion of Dagla in neural stem and progenitor cells (NSPCs) and astrocytes (GLAST-CreERT2-Dagla KO) led to a 50% decrease in the proliferation of newborn cells in the dentate gyrus, indicating its role in adult hippocampal neurogenesis [4]. Astrocytic deletion of Dagla (GLAST-Dagla KO) in female mice decreased acute hedonic appetite for palatable food, potentially due to an altered female sex hormone profile [3]. In addition, knockdown of DAGLA in oral squamous cell carcinoma (OSCC) cell lines led to depressed cellular functions like proliferation and migratory activities through cell-cycle arrest at G1 phase [5].

In conclusion, DAGLA plays significant roles in multiple biological processes. The use of KO mouse models has revealed its importance in adult hippocampal neurogenesis, hedonic feeding in females, and tumorigenesis in oral cancer. These findings provide insights into the mechanisms underlying these processes and suggest potential therapeutic targets for related diseases [3,4,5].

References:

1. Yan, Yu-Chuan, Meng, Guang-Xiao, Yang, Chun-Cheng, Dong, Zhao-Ru, Li, Tao. 2023. Diacylglycerol lipase alpha promotes hepatocellular carcinoma progression and induces lenvatinib resistance by enhancing YAP activity. In Cell death & disease, 14, 404. doi:10.1038/s41419-023-05919-5. https://pubmed.ncbi.nlm.nih.gov/37414748/

2. Bainbridge, Matthew N, Mazumder, Aloran, Ogasawara, Daisuke, Torkamani, Ali, Friedman, Jennifer. . Endocannabinoid dysfunction in neurological disease: neuro-ocular DAGLA-related syndrome. In Brain : a journal of neurology, 145, 3383-3390. doi:10.1093/brain/awac223. https://pubmed.ncbi.nlm.nih.gov/35737950/

3. Leidmaa, Este, Prodan, Alexandra Maria, Depner, Lena-Louise, Kolbe, Carl-Christian, Zimmer, Andreas. 2024. Astrocytic Dagla Deletion Decreases Hedonic Feeding in Female Mice. In Cannabis and cannabinoid research, 9, 74-88. doi:10.1089/can.2023.0194. https://pubmed.ncbi.nlm.nih.gov/38265773/

4. Schuele, Lena-Louise, Schuermann, Britta, Bilkei-Gorzo, Andras, Zimmer, Andreas, Leidmaa, Este. 2022. Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa). In Scientific reports, 12, 633. doi:10.1038/s41598-021-04600-1. https://pubmed.ncbi.nlm.nih.gov/35022487/

5. Okubo, Yasuhiko, Kasamatsu, Atsushi, Yamatoji, Masanobu, Tanzawa, Hideki, Uzawa, Katsuhiro. 2018. Diacylglycerol lipase alpha promotes tumorigenesis in oral cancer by cell-cycle progression. In Experimental cell research, 367, 112-118. doi:10.1016/j.yexcr.2018.03.041. https://pubmed.ncbi.nlm.nih.gov/29614312/