Jcad-KO Mouse

JCAD, also known as junctional cadherin 5 associated, is an endothelial cell-cell junction protein. It has been implicated in multiple biological processes, with its expression associated with cardiovascular diseases such as atherosclerosis and hypertension. JCAD is involved in pathways like PI3K/Akt, LATS2/Hippo, and YAP/TAZ, influencing cell proliferation, coagulation, and fibrosis [1,2,3,4]. Genetic models, especially knockout (KO) mice, have been crucial in studying its functions.

In KO mouse models, Jcad -/- mice showed reduced thrombogenicity due to decreased activation of the coagulation cascade and increased fibrinolysis, suggesting JCAD promotes arterial thrombosis by modulating these processes [1]. JCAD deficiency also attenuated hepatic fibrosis induced by bile duct ligation in mice, mainly through suppressing Hippo-YAP signaling activity in hepatic stellate cells [2]. Additionally, both global and liver-specific JCAD deficiency postponed liver regeneration after partial hepatectomy, as JCAD competes with LATS2 for WWC1 interaction, affecting the Hippo-YAP signaling pathway and cell cycle-associated genes [3]. In ApoE-deficient mice, JCAD deficiency attenuated high-fat diet-induced atherosclerosis and improved endothelium-dependent relaxation, with JCAD depletion in human coronary artery endothelial cells inhibiting YAP/TAZ pathway activation and downstream pro-atherogenic gene expression [4].

In conclusion, JCAD plays essential roles in thrombosis, hepatic fibrosis, liver regeneration, and atherosclerosis. Studies using JCAD KO mouse models have provided valuable insights into these disease-related biological processes, highlighting JCAD as a potential therapeutic target for atherothrombosis and cholestatic liver diseases [1,2].

References:

1. Liberale, Luca, Puspitasari, Yustina M, Ministrini, Stefano, Lüscher, Thomas F, Camici, Giovanni G. . JCAD promotes arterial thrombosis through PI3K/Akt modulation: a translational study. In European heart journal, 44, 1818-1833. doi:10.1093/eurheartj/ehac641. https://pubmed.ncbi.nlm.nih.gov/36469488/

2. Xie, Li, Chen, Hui, Zhang, Li, Liu, Xiu-Ping, Wu, Jian. 2024. JCAD deficiency attenuates activation of hepatic stellate cells and cholestatic fibrosis. In Clinical and molecular hepatology, 30, 206-224. doi:10.3350/cmh.2023.0506. https://pubmed.ncbi.nlm.nih.gov/38190829/

3. Zhang, Li, Yang, Yong-Yu, Xie, Li, Yu, Fa-Xing, Wu, Jian. . JCAD deficiency delayed liver regenerative repair through the Hippo-YAP signalling pathway. In Clinical and translational medicine, 14, e1630. doi:10.1002/ctm2.1630. https://pubmed.ncbi.nlm.nih.gov/38509842/

4. Xu, Suowen, Xu, Yanni, Liu, Peng, Miller, Clint L, Jin, Zheng Gen. . The novel coronary artery disease risk gene JCAD/KIAA1462 promotes endothelial dysfunction and atherosclerosis. In European heart journal, 40, 2398-2408. doi:10.1093/eurheartj/ehz303. https://pubmed.ncbi.nlm.nih.gov/31539914/