Kdm6b-KO Mouse

Kdm6b, also known as JMJD3, is a histone demethylase that specifically removes methyl groups from H3K27me3, thus allowing re-expression of its target genes. This function is crucial in regulating gene expression and is involved in various biological processes such as cell differentiation, development, and disease-related pathways [3]. Genetic models, like KO/CKO mouse models, are valuable in studying its functions.

In osteosarcoma, high Kdm6B expression is associated with poorer prognosis, and targeting it inhibits cell migration and lung metastasis. Kdm6B increases lactate dehydrogenase LDHA expression by mediating H3K27me3 demethylation [1]. In glioblastoma, myeloid-specific Kdm6b deletion enhances pro-inflammatory pathways and improves survival in tumor-bearing mice, as it inhibits mediators of immune suppression [2]. In T-cell acute lymphoblastic leukemia (T-ALL), mouse cells genetically deficient for Kdm6b cannot propagate T-ALL, and inactivating KDM6B in human patient cells leads to their out-competition over time, suggesting Kdm6B is required for T-ALL development and maintenance [4].

In conclusion, Kdm6b plays essential roles in multiple biological processes and disease conditions. Model-based research, especially KO/CKO mouse models, has revealed its significance in cancer-related diseases such as osteosarcoma, glioblastoma, and T-ALL, providing potential therapeutic targets for these diseases.

References:

1. Jiang, Yuhang, Li, Fengfeng, Gao, Bowen, Liu, Sanhong, Shen, Huiyong. 2021. KDM6B-mediated histone demethylation of LDHA promotes lung metastasis of osteosarcoma. In Theranostics, 11, 3868-3881. doi:10.7150/thno.53347. https://pubmed.ncbi.nlm.nih.gov/33664867/

2. Goswami, Sangeeta, Raychaudhuri, Deblina, Singh, Pratishtha, Basu, Sreyashi, Sharma, Padmanee. 2023. Myeloid-specific KDM6B inhibition sensitizes glioblastoma to PD1 blockade. In Nature cancer, 4, 1455-1473. doi:10.1038/s43018-023-00620-0. https://pubmed.ncbi.nlm.nih.gov/37653141/

3. Lagunas-Rangel, Francisco Alejandro. 2021. KDM6B (JMJD3) and its dual role in cancer. In Biochimie, 184, 63-71. doi:10.1016/j.biochi.2021.02.005. https://pubmed.ncbi.nlm.nih.gov/33581195/

4. Issa, Nancy, Bjeije, Hassan, Wilson, Elisabeth R, Spencer, David H, Challen, Grant A. 2023. KDM6B protects T-ALL cells from NOTCH1-induced oncogenic stress. In Leukemia, 37, 728-740. doi:10.1038/s41375-023-01853-9. https://pubmed.ncbi.nlm.nih.gov/36797416/