Camk2g, encoding the gamma subunit of calcium/calmodulin-dependent protein kinase 2, is expressed throughout the brain and is involved in multiple biological processes. It functions in signal transduction pathways, with its activation being associated with various cellular responses. Genetic models, such as knockout mice, are valuable for studying its role [2,4].

In myelofibrosis (MF), Camk2g was identified as a novel therapeutic target. In MF model cells and mice, Camk2g inhibition was effective against both JAK2 inhibitor-sensitive and resistant cells. Berbamine, a Camk2g inhibitor, prolonged survival and reduced disease phenotypes in an MF mouse model. Camk2g is activated by MPL signaling and is an effector in the MPL-JAK2 signaling pathway in MF cells [1].

In Camk2g knockout mice, different isoforms were found with distinct spatial expression patterns in the brain. Loss of Camk2g affects motor function and innate behaviors like nest-building and marble burying, but has minimal impact on hippocampus-dependent learning and synaptic plasticity [2].

In neuroblastoma, knockdown of Camk2g inhibited neuronal differentiation and promoted migration, invasion, and proliferation [3].

In conclusion, Camk2g plays essential roles in multiple biological processes. Its study using knockout mouse models has revealed its significance in diseases such as myelofibrosis, as well as in brain-related functions including motor behavior and neurodevelopment. These findings provide potential therapeutic strategies for certain diseases and enhance our understanding of normal and abnormal biological functions [1,2,3].

References:

1. Miyauchi, Masashi, Sasaki, Ken, Kagoya, Yuki, Mizuno, Hideaki, Kurokawa, Mineo. . CAMK2G is identified as a novel therapeutic target for myelofibrosis. In Blood advances, 6, 1585-1597. doi:10.1182/bloodadvances.2020003303. https://pubmed.ncbi.nlm.nih.gov/34521112/

2. Rigter, Pomme M F, de Konink, Charlotte, van Woerden, Geeske M. 2023. Loss of CAMK2G affects intrinsic and motor behavior but has minimal impact on cognitive behavior. In Frontiers in neuroscience, 16, 1086994. doi:10.3389/fnins.2022.1086994. https://pubmed.ncbi.nlm.nih.gov/36685241/

3. Ma, Yujie, He, Cong, Lin, Weihong, Jia, Deshui, Li, Kai. 2024. CAMK2G Promotes Neuronal Differentiation and Inhibits Migration in Neuroblastoma. In Journal of pediatric surgery, 60, 161679. doi:10.1016/j.jpedsurg.2024.08.019. https://pubmed.ncbi.nlm.nih.gov/39266386/

4. Proietti Onori, Martina, Koopal, Balwina, Everman, David B, Elgersma, Ype, van Woerden, Geeske M. 2018. The intellectual disability-associated CAMK2G p.Arg292Pro mutation acts as a pathogenic gain-of-function. In Human mutation, 39, 2008-2024. doi:10.1002/humu.23647. https://pubmed.ncbi.nlm.nih.gov/30184290/