Hnrnpk-flox Mouse

Hnrnpk, or heterogeneous nuclear ribonucleoprotein K, is a DNA/RNA-binding protein containing 3 K-homologous (KH) domains. It functions as an enhancer or repressor of gene transcription, and phosphorylation can alter its regulatory function, allowing it to serve as a docking platform for signal transduction proteins. Hnrnpk is involved in many cellular events, such as long non-coding RNA (lncRNA) regulation, cancer development, and bone homeostasis [1].

Deletion of Hnrnpk in mice accelerates the development of post-traumatic and age-dependent osteoarthritis (OA) by increasing WWC1 expression and activating the Hippo signaling pathway, indicating its role in maintaining articular cartilage homeostasis [2]. In hepatic progenitor cells, TNFR2-hnRNPK-YAP signaling axis is essential for primary liver cancer development, with hnRNPK acting downstream of TNFα-TNFR2 to interact with and stabilize YAP on target gene promoters [3]. Ablating Hnrnpk in mice causes dwarfism due to damaged survival and premature differentiation of growth plate chondrocytes, as it regulates the Hif1α-glycolysis axis by binding to Hif1a mRNA and promoting its degradation [4].

In summary, Hnrnpk is crucial for maintaining cellular and tissue homeostasis. Gene knockout mouse models have revealed its important roles in OA, primary liver cancer, and skeletal development. Understanding Hnrnpk's functions can provide insights into the mechanisms of these diseases and potential therapeutic targets.