Cltc-KO Mouse

Cltc, encoding the clathrin heavy chain protein, is crucial for clathrin-mediated endocytosis, a process by which cells internalize extracellular materials. This pathway is involved in various cellular functions such as receptor-mediated transport, signal transduction, and viral entry. Understanding Cltc's function is important for deciphering normal cellular processes and disease mechanisms [2,5].

De novo Cltc variants are associated with a wide range of phenotypes from mild to severe intellectual disability, often accompanied by microcephaly, hypoplasia of the corpus callosum, and epilepsy [1]. Novel Cltc variants have also been found to cause new brain and kidney phenotypes, including cystic lesions in the brain, high-echogenic kidneys, and kidney agenesis [3]. In osteosarcoma, high expression of Cltc is an independent prognostic factor, and its down-regulation has tumor-suppressive effects, interacting with TFG via the TGF-β and AKT/mTOR signaling pathways [4]. Additionally, knockout of the Cltc gene reduces but does not completely block SFTSV infection, indicating that clathrin-dependent and lipid raft-mediated endocytosis are major entry modes for SFTSV [2].

In conclusion, Cltc is essential for clathrin-mediated endocytosis and is involved in multiple biological processes. Research on Cltc, especially through gene knockout studies, has revealed its significance in neurodevelopmental disorders, viral infections, and cancer, providing insights into disease mechanisms and potential therapeutic targets.