Pwp1-KO Mouse

Pwp1, also known as Periodic tryptophan protein 1 homolog or endonuclein, is a chromatin - binding protein with diverse functions. It is involved in multiple essential biological processes, such as telomere length regulation, ribosome biogenesis, and the regulation of signaling pathways like Wnt and Hippo. It also plays a role in cell differentiation, development, and nutrient - dependent growth control [2,3,4,5,6].

Homozygous Pwp1 - knockout mice and embryonic stem cells (ESCs) have never been obtained, indicating its essentiality for mouse development and ESC survival. Heterozygous Pwp1 - knockout mice had shorter telomeres and decreased reproductive capacity. Pwp1 depletion induced rapid telomere shortening, reduced shelterin complex, and increased DNA damage in telomeric regions [2]. In mouse embryonic stem cells (mESCs), knockdown of Pwp1 impairs their differentiation potential both in vitro and in vivo [5]. In mouse preimplantation embryos, Pwp1 inhibition reduces developmental potential and causes irregular localization of YAP1, abnormal regulation of inner cell mass and trophectoderm markers, and upregulation of ZGA gene expression [8]. In cancer, PWP1 is overexpressed in hepatocellular carcinoma, lung cancer, and gastric cancer, promoting cancer cell proliferation, invasion, and metastasis. For example, siRNA - mediated PWP1 silencing significantly suppressed HCC cell proliferation in vitro [1,3,7].

In conclusion, Pwp1 is crucial for various biological functions including telomere maintenance, cell differentiation, and ribosome biogenesis. The study of Pwp1 knockout models has revealed its significant roles in development and disease, especially in cancer. These findings suggest that Pwp1 could be a potential therapeutic target for treating certain cancers [1,2,3,5,7,8].