Prdm15-KO Mouse

PRDM15, a member of the PRDM (PRDI-BF1 and RIZ homology domain containing) family, is a transcriptional regulator. It has been implicated in multiple biological processes such as cell identity and fate determination. It is involved in pathways like DNA damage repair, metabolism regulation, and signaling pathways including WNT and MAPK-ERK [1,2,4]. Its low expression in adult tissues and overexpression in certain cancers make it a gene of interest in oncology research. Genetic models, especially gene knockout models, have been crucial in understanding its functions.

In rectal cancer, knockdown of PRDM15 inhibited DNA damage repair, increased radiosensitivity, and sensitized xenograft models to radiotherapy, indicating its role in promoting radioresistance through facilitating DNA repair [1]. In B-cell lymphomas, ablation of PRDM15 induced a metabolic crisis and selective death of lymphoma cells as it regulates a transcriptional program sustaining the PI3K/AKT/mTOR pathway and glycolysis [2]. In Xenopus embryos, morpholino-mediated knockdown of Prdm15 disrupted pronephric development, and in human podocytes, CRISPR-mediated knockout led to dysregulation of renal developmental genes, suggesting its role in renal development [3]. In mouse embryonic stem cells, disruption of PRDM15-binding sites in the Rspo1 and Spry1 promoters recapitulated PRDM15 depletion, affecting local chromatin organization and gene transcription, highlighting its role in safeguarding naive pluripotency [4].

In summary, PRDM15 plays essential roles in DNA damage repair, metabolism in cancer cells, renal development, and maintaining naive pluripotency. The use of gene knockout models in these studies has provided valuable insights into its functions in rectal cancer, B-cell lymphomas, and renal-related diseases, helping to understand the underlying mechanisms and potentially identify new therapeutic targets.

References:

1. Yu, Yue, Liu, Tingting, Yu, Guanyu, Yang, Yanyong, Zhang, Wei. 2022. PRDM15 interacts with DNA-PK-Ku complex to promote radioresistance in rectal cancer by facilitating DNA damage repair. In Cell death & disease, 13, 978. doi:10.1038/s41419-022-05402-7. https://pubmed.ncbi.nlm.nih.gov/36402747/

2. Mzoughi, Slim, Fong, Jia Yi, Papadopoli, David, Topisirovic, Ivan, Guccione, Ernesto. 2020. PRDM15 is a key regulator of metabolism critical to sustain B-cell lymphomagenesis. In Nature communications, 11, 3520. doi:10.1038/s41467-020-17064-0. https://pubmed.ncbi.nlm.nih.gov/32665551/

3. Mann, Nina, Mzoughi, Slim, Schneider, Ronen, Zenker, Martin, Hildebrandt, Friedhelm. 2021. Mutations in PRDM15 Are a Novel Cause of Galloway-Mowat Syndrome. In Journal of the American Society of Nephrology : JASN, 32, 580-596. doi:10.1681/ASN.2020040490. https://pubmed.ncbi.nlm.nih.gov/33593823/

4. Mzoughi, Slim, Zhang, Jingxian, Hequet, Delphine, Messerschmidt, Daniel M, Guccione, Ernesto. 2017. PRDM15 safeguards naive pluripotency by transcriptionally regulating WNT and MAPK-ERK signaling. In Nature genetics, 49, 1354-1363. doi:10.1038/ng.3922. https://pubmed.ncbi.nlm.nih.gov/28740264/