Dab2-KO Mouse

Dab2, also known as Disabled-2 or DOC-2, is a mitogen-responsive adaptor protein essential for multiple cellular functions. It plays a crucial role in clathrin-mediated endocytosis and is involved in key signalling pathways such as mitogen-activated protein kinase (MAPK), wingless/integrated (Wnt), and transforming growth factor beta (TGFβ) pathways, which are related to homeostasis, cell positioning, and epithelial to mesenchymal transition (EMT) [1,2].

In a Dab2 conditional knockout (Dab2-cKO) mouse model, the hair follicle (HF) cycle was delayed due to perturbed activation of HF stem cells (HFSCs). The number of HFSCs and their colony-forming ability were reduced. The HFSCs in Dab2-cKO mice showed extended quiescence, and the expression of anti-aging genes decreased, suggesting an accelerated aging process. This reveals the role of Dab2 in regulating the activation and self-renewal of HFSCs [3].

In another study, knockdown of DAB2 in human lung fibroblast MRC-5 cells treated with TGF-β1 suppressed cell proliferation and the expression of fibrosis-related proteins. This indicates that DAB2 may play a role in promoting pulmonary fibrosis [4].

In conclusion, Dab2 is a multifunctional protein involved in various cellular functions and signalling pathways. Model-based research, especially the Dab2-cKO mouse model, has revealed its role in processes like HFSC self-renewal and in disease conditions such as pulmonary fibrosis. These findings contribute to understanding the biological functions of Dab2 and its potential implications in disease development.