Camk1d-KO Mouse

Camk1d, or calcium/calmodulin-dependent protein kinase ID, is involved in intracellular signaling. It has been associated with multiple biological processes and disease-related pathways [2,3,4,5,6,7]. Genetic models, such as knockout mouse models, have been crucial in studying its functions.

Global Camk1d-knockout male mice are resistant to ghrelin, gain less body weight, and are protected against high-fat-diet-induced obesity. Deletion of Camk1d in AgRP/NPY, but not in POMC, neurons recapitulates these phenotypes. Lack of CaMK1D attenuates phosphorylation of CREB and CREB-dependent expression of orexigenic neuropeptides in AgRP neurons in response to ghrelin [1]. In glioma, knockdown of CAMK1D promotes cell proliferation, invasion, and migration, while overexpression has opposite effects, suggesting it inhibits glioma through the PI3K/AKT/mTOR pathway [2].

In conclusion, Camk1d is important in regulating food intake via its role in AgRP neurons and in influencing glioma cell behavior. The gene knockout mouse models have provided valuable insights into its functions in obesity-related and cancer-related disease areas.

References:

1. Vivot, Karl, Meszaros, Gergö, Pangou, Evanthia, Nogueiras, Ruben, Ricci, Romeo. 2023. CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake. In Nature metabolism, 5, 1045-1058. doi:10.1038/s42255-023-00814-x. https://pubmed.ncbi.nlm.nih.gov/37277610/

2. Jin, Qianxu, Zhao, Jiahui, Zhao, Zijun, Liu, Liping, Zhao, Zongmao. 2022. CAMK1D Inhibits Glioma Through the PI3K/AKT/mTOR Signaling Pathway. In Frontiers in oncology, 12, 845036. doi:10.3389/fonc.2022.845036. https://pubmed.ncbi.nlm.nih.gov/35494053/

3. Volpin, Valentina, Michels, Tillmann, Sorrentino, Antonio, Khandelwal, Nisit, Beckhove, Philipp. 2020. CAMK1D Triggers Immune Resistance of Human Tumor Cells Refractory to Anti-PD-L1 Treatment. In Cancer immunology research, 8, 1163-1179. doi:10.1158/2326-6066.CIR-19-0608. https://pubmed.ncbi.nlm.nih.gov/32665263/

4. Xue, Angli, Wu, Yang, Zhu, Zhihong, Zeng, Jian, Yang, Jian. 2018. Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. In Nature communications, 9, 2941. doi:10.1038/s41467-018-04951-w. https://pubmed.ncbi.nlm.nih.gov/30054458/

5. Du, Bingxin, Jia, Xinhui, Tian, Wenqi, Qiu, Changchun, Zhang, Qi. 2020. Associations of SUCNR1, GRK4, CAMK1D gene polymorphisms and the susceptibility of type 2 diabetes mellitus and essential hypertension in a northern Chinese Han population. In Journal of diabetes and its complications, 35, 107752. doi:10.1016/j.jdiacomp.2020.107752. https://pubmed.ncbi.nlm.nih.gov/33127268/

6. Strausz, Satu, Ruotsalainen, Sanni, Ollila, Hanna M, Palotie, Tuula, Ripatti, Samuli. 2021. Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health. In The European respiratory journal, 57, . doi:10.1183/13993003.03091-2020. https://pubmed.ncbi.nlm.nih.gov/33243845/

7. Bergamaschi, Anna, Kim, Young H, Kwei, Kevin A, Børresen-Dale, Anne-Lise, Pollack, Jonathan R. 2008. CAMK1D amplification implicated in epithelial-mesenchymal transition in basal-like breast cancer. In Molecular oncology, 2, 327-39. doi:10.1016/j.molonc.2008.09.004. https://pubmed.ncbi.nlm.nih.gov/19383354/