Pdcd10-KO Mouse

Pdcd10, also known as CCM3, was initially identified as an apoptosis-related gene. It is a key gene in maintaining cell homeostasis, with multiple subcellular localizations. Pdcd10 interacts with several multi-protein complexes and signaling pathways, governing various cellular functions such as cell-to-cell junctions, cytoskeleton organization, cell proliferation, apoptosis, exocytosis, and angiogenesis [1].

In kidney tubules, Pdcd10-deficient mice developed polyuria and increased water consumption. Pdcd10 forms a complex with GCKIII kinases, and its deficiency led to decreased levels of total and phosphorylated aquaporin 2 (Aqp2) protein in the apical membrane of tubular epithelial cells, associated with increased Ezrin and p-ERM proteins and impaired intracellular vesicle trafficking. This indicates Pdcd10's role in kidney water reabsorption via regulating Aqp2 membrane targeting [2]. In glioblastoma, knockdown of Pdcd10 upregulated EphB4, accompanied by Erk1/2 activation, promoting tumor cell proliferation, neo-angiogenesis, and tumor progression. Targeting EphB4 might be an effective strategy for Pdcd10-deficient glioblastoma patients [3].

In summary, Pdcd10 is crucial for multiple cellular functions. Gene-knockout mouse models have revealed its roles in specific biological processes like kidney water balance and in disease conditions such as glioblastoma, contributing to a better understanding of related physiological and pathological mechanisms.

References:

1. Valentino, Mariaelena, Dejana, Elisabetta, Malinverno, Matteo. 2020. The multifaceted PDCD10/CCM3 gene. In Genes & diseases, 8, 798-813. doi:10.1016/j.gendis.2020.12.008. https://pubmed.ncbi.nlm.nih.gov/34522709/

2. Wang, Rui, Wu, Shi-Ting, Yang, Xi, Xia, Yin, Zheng, Xiangjian. 2021. Pdcd10-Stk24/25 complex controls kidney water reabsorption by regulating Aqp2 membrane targeting. In JCI insight, 6, . doi:10.1172/jci.insight.142838. https://pubmed.ncbi.nlm.nih.gov/34156031/

3. Wan, Xueyan, Saban, Dino Vitali, Kim, Su Na, Sure, Ulrich, Zhu, Yuan. 2020. PDCD10-Deficiency Promotes Malignant Behaviors and Tumor Growth via Triggering EphB4 Kinase Activity in Glioblastoma. In Frontiers in oncology, 10, 1377. doi:10.3389/fonc.2020.01377. https://pubmed.ncbi.nlm.nih.gov/32850441/