Klf17-KO Mouse

Klf17, a member of the Krüppel-like factor (KLF) family of transcription factors, is involved in multiple biological processes. It plays crucial roles in zygotic genome activation (ZGA), pluripotency maintenance, and may be associated with various diseases [1-3]. In ZGA, it acts as a messenger for RNA Pol II recruitment, while in pluripotency, it promotes the naive state in human embryonic stem cells (hESCs) through repressing certain target genes [1-3].

In a conditional knockout (cKO) mouse model, maternal Klf17 was found to promote embryonic development and full fertility. Maternal Klf17 knockout led to a down-regulation of 9% of ZGA genes and abnormal RNA Pol II pre-configuration, which could be partially rescued by exogenous KLF17, highlighting its importance in ZGA [1]. In human hESCs, loss-of-function approaches demonstrated that KLF17 is essential for maintaining the naive state and promoting the primed to naive state transition, by repressing MAPK3 and ZIC2 [2]. However, CRISPR-Cas9-mediated knockout studies in hESCs showed that KLF17 is not required for naive pluripotency acquisition in vitro, though it has subtle effects on metabolism and signalling pathways [3].

In conclusion, Klf17 is a key factor in ZGA and pluripotency regulation. The use of gene knockout mouse models has revealed its significance in early embryo development and pluripotency-related processes. Additionally, its down-regulation in gastric and colorectal cancers suggests potential roles in cancer-related processes, though more research is needed to fully understand its implications in disease [1-3].

References:

1. Hu, Yue, Wang, Yuxiang, He, Yuanlin, Shu, Wenjie, Huo, Ran. 2024. Maternal KLF17 controls zygotic genome activation by acting as a messenger for RNA Pol II recruitment in mouse embryos. In Developmental cell, 59, 613-626.e6. doi:10.1016/j.devcel.2024.01.013. https://pubmed.ncbi.nlm.nih.gov/38325372/

2. Wang, Shao-Hua, Hao, Jing, Zhang, Chao, Cao, Huiqing, Wang, Yangming. 2022. KLF17 promotes human naive pluripotency through repressing MAPK3 and ZIC2. In Science China. Life sciences, 65, 1985-1997. doi:10.1007/s11427-021-2076-x. https://pubmed.ncbi.nlm.nih.gov/35391627/

3. Lea, Rebecca A, McCarthy, Afshan, Boeing, Stefan, Taranissi, Mohamed, Niakan, Kathy K. 2021. KLF17 promotes human naïve pluripotency but is not required for its establishment. In Development (Cambridge, England), 148, . doi:10.1242/dev.199378. https://pubmed.ncbi.nlm.nih.gov/34661235/