Jade2-KO Mouse

Jade2, also known as PHF16, is an epigenetic factor that plays a crucial role in various biological processes. It is a core subunit of the HBO1 acetyltransferase complex, regulating developmental and epigenetic programs and promoting gene transcription [5]. It is involved in pathways related to synaptic plasticity, cell cycle progression, cell regeneration, and the DNA damage response [2,6]. Genetic models, such as KO/CKO mouse models, have been valuable in studying its functions.

In mice, knockdown or genetic deletion of Jade2 in hippocampal CA1 results in impaired structural and functional synaptic plasticity, leading to memory impairment. Conversely, overexpression of Jade2 in CA1 neurons facilitates hippocampal-dependent learning and memory. Mechanistically, Jade2 modulates synaptic functions mainly by transcriptional activation of cytoskeletal regulator Rac1, and this activity depends on its interaction with histone acetyltransferase HBO1. Restoring RAC1 expression in Jade2 knockout mice could rescue the deficits in synaptic plasticity and learning-related behaviors, revealing its critical role in regulating synaptic plasticity and memory formation [1].

In non-small cell lung cancer (NSCLC), high expression of Jade2 is associated with a better 5-year overall survival, suggesting its potential clinical utility in diagnosis, prognosis, and patient stratification [2]. In an AML patient with APL-like features, a NUP98-Jade2 fusion was identified, which could impair all-trans retinoic acid (ATRA)-mediated transcriptional control and myeloid differentiation, suggesting Jade2 as a novel myeloid player involved in retinoic acid-induced differentiation [3]. In severe acute pancreatitis (SAP), Jade2 is one of the hub genes identified, potentially playing important roles in SAP progression as it is highly correlated with multiple immune cells, regulating immune cell infiltration in the microenvironment [4]. In HBV-related acute-on-chronic liver failure (HBV-ACLF), the mir-6840-3p-Jade2 pair may promote the progression of ACLF and lead to poor prognosis [7]. In pediatric brain tumors, an eight-gene signature including Jade2 could accurately identify patients' prognosis and had close interactions with the immunodominant tumor environment [8].

In conclusion, Jade2 is essential for hippocampal synaptic plasticity and cognitive functions in mice. Its role in diseases such as NSCLC, AML with APL-like features, SAP, HBV-ACLF, and pediatric brain tumors has been revealed through model-based research. These findings contribute to our understanding of the biological functions of Jade2 and its potential as a therapeutic target in these disease areas.

References:

1. Fan, Minghua, Liu, Yongqing, Shang, Yongfeng, Liang, Jing, Huang, Zhuo. 2022. JADE2 Is Essential for Hippocampal Synaptic Plasticity and Cognitive Functions in Mice. In Biological psychiatry, 92, 800-814. doi:10.1016/j.biopsych.2022.05.021. https://pubmed.ncbi.nlm.nih.gov/36008159/

2. Murphy, Ciara, Gornés Pons, Glòria, Keogh, Anna, Finn, Stephen P, Gray, Steven G. 2023. An Analysis of JADE2 in Non-Small Cell Lung Cancer (NSCLC). In Biomedicines, 11, . doi:10.3390/biomedicines11092576. https://pubmed.ncbi.nlm.nih.gov/37761019/

3. Cheng, Chi-Keung, Chan, Hoi-Yun, Yung, Yuk-Lin, Cheung, Joyce S, Ng, Margaret H L. . A novel NUP98-JADE2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia. In Blood advances, 6, 410-415. doi:10.1182/bloodadvances.2021006064. https://pubmed.ncbi.nlm.nih.gov/34673934/

4. Xiao, Shuai, Han, Xiao, Bai, Shuhui, Chen, Rui. 2024. Analysis of immune cell infiltration characteristics in severe acute pancreatitis through integrated bioinformatics. In Scientific reports, 14, 8711. doi:10.1038/s41598-024-59205-1. https://pubmed.ncbi.nlm.nih.gov/38622245/

5. Gaurav, Nitika, Kanai, Akinori, Lachance, Catherine, Yokoyama, Akihiko, Kutateladze, Tatiana G. 2024. Guiding the HBO1 complex function through the JADE subunit. In Nature structural & molecular biology, 31, 1039-1049. doi:10.1038/s41594-024-01245-2. https://pubmed.ncbi.nlm.nih.gov/38448574/

6. Panchenko, Maria V. 2016. Structure, function and regulation of jade family PHD finger 1 (JADE1). In Gene, 589, 1-11. doi:10.1016/j.gene.2016.05.002. https://pubmed.ncbi.nlm.nih.gov/27155521/

7. Ma, Shanshan, Xie, Zhongyang, Zhang, Lingjian, Xu, Xiaowei, Li, Lanjuan. 2021. Identification of a Potential miRNA-mRNA Regulatory Network Associated With the Prognosis of HBV-ACLF. In Frontiers in molecular biosciences, 8, 657631. doi:10.3389/fmolb.2021.657631. https://pubmed.ncbi.nlm.nih.gov/33996909/

8. Wang, Yi, Zhou, Chuan, Luo, Huan, Cheng, Lulu, Yang, Yang. 2021. Prognostic implications of immune-related eight-gene signature in pediatric brain tumors. In Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas, 54, e10612. doi:10.1590/1414-431X2020e10612. https://pubmed.ncbi.nlm.nih.gov/34008756/