Stab1-KO Mouse

Stab1, encoding the multifunctional scavenger receptor stabilin-1, is preferentially expressed by liver sinusoidal endothelial cells. It mediates the clearance of circulating plasma molecules, thus controlling distant organ homeostasis. It may be involved in multiple pathways, and its dysregulation has implications for various biological processes [1,4].

In ApoE-KO mice interbred with Stab1-KO mice, spontaneous and Western diet-associated atherogenesis was significantly reduced. Inhibition of Stab1 by monoclonal antibodies also decreased Western diet-associated atherosclerosis in ApoE-KO and Ldlr-KO mice. Plasma proteomics showed a switch in the plasma proteome, and single-cell RNA sequencing indicated transcriptomic alterations in monocytes, suggesting that Stab1 affects atherogenesis through modulating the plasma proteome and monocyte behavior [1].

In acute myeloid leukemia (AML), STAB1 knockdown in human AML cell lines HEL and NB4 suppressed proliferation and promoted apoptosis through regulating the IKK/NF-κB pathway. In xenograft mouse models, STAB1 silencing prolonged survival and reduced the aggressiveness of AML cells. Also, co-culture of macrophages with conditioned medium from STAB1-knockdown AML cells reduced M2 polarization of macrophages [2]. In cytogenetically normal AML, high STAB1 expression is associated with poor outcomes, and STAB1 suppression inhibits cell growth in leukemia cells [3].

In summary, Stab1 plays a significant role in atherogenesis and AML progression. Gene-knockout mouse models have been crucial in revealing these functions, providing insights into its role in disease-related biological processes and suggesting Stab1 as a potential therapeutic target for atherosclerosis and AML.

References:

1. Manta, Calin-Petru, Leibing, Thomas, Friedrich, Mirco, Goerdt, Sergij, Géraud, Cyrill. 2022. Targeting of Scavenger Receptors Stabilin-1 and Stabilin-2 Ameliorates Atherosclerosis by a Plasma Proteome Switch Mediating Monocyte/Macrophage Suppression. In Circulation, 146, 1783-1799. doi:10.1161/CIRCULATIONAHA.121.058615. https://pubmed.ncbi.nlm.nih.gov/36325910/

2. Yin, Jiaxiu, Luo, Jing, Wang, Lan, Liu, Lanxiang, Liu, Lin. 2025. STAB1 Promotes Acute Myeloid Leukemia Progression by Activating the IKK/NF-κB Pathway and Increasing M2 Macrophage Polarization. In Cancer science, , . doi:10.1111/cas.70044. https://pubmed.ncbi.nlm.nih.gov/40083109/

3. Lin, Sheng-Yan, Hu, Fei-Fei, Miao, Ya-Ru, Chen, Zhichao, Guo, An-Yuan. 2019. Identification of STAB1 in Multiple Datasets as a Prognostic Factor for Cytogenetically Normal AML: Mechanism and Drug Indications. In Molecular therapy. Nucleic acids, 18, 476-484. doi:10.1016/j.omtn.2019.09.014. https://pubmed.ncbi.nlm.nih.gov/31670197/

4. Monfrini, Edoardo, Pelucchi, Sara, Hollmén, Maija, Di Fonzo, Alessio, Piperno, Alberto. 2023. A form of inherited hyperferritinemia associated with bi-allelic pathogenic variants of STAB1. In American journal of human genetics, 110, 1436-1443. doi:10.1016/j.ajhg.2023.07.004. https://pubmed.ncbi.nlm.nih.gov/37490907/