Clec4e-KO Mouse

Clec4e, also known as Mincle, is a C-type lectin domain family 4 member. It is involved in the body's immune response, particularly in sterile inflammation [1,2,3]. It is part of the host's first-line defense when encountering pathogens, and its signaling pathways are associated with innate immunity [2,3]. Genetic models, such as gene knockout mouse models, are valuable for studying its function.

In a KO mouse model, loss of Clec4e signaling led to reduced acute cardiac injury, neutrophil infiltration, and infarct size after ischemia-reperfusion injury. This translated into improved left ventricular structural and functional remodeling at 4-week follow-up. The early transcriptome of KO mice showed upregulation of transcripts related to myocardial metabolism, radical scavenging, angiogenesis, and extracellular matrix organization [1]. In another study, Clec4e -/- mice had impaired trained immunity induced by Enterococcus faecalis and reduced pathology following dextran sulfate sodium treatment, indicating its importance in microbiota-mediated training of myeloid progenitors in the bone marrow [4].

In conclusion, Clec4e plays a crucial role in the immune response, affecting processes like sterile inflammation, myocardial repair after ischemia-reperfusion injury, and training of myeloid progenitors. Gene knockout mouse models have been instrumental in revealing these functions, providing insights into its role in specific disease areas such as cardiac injury and conditions related to increased gut permeability.

References:

1. Veltman, Denise, Wu, Ming, Pokreisz, Peter, Sinnaeve, Peter R, Janssens, Stefan P. 2021. Clec4e-Receptor Signaling in Myocardial Repair After Ischemia-Reperfusion Injury. In JACC. Basic to translational science, 6, 631-646. doi:10.1016/j.jacbts.2021.07.001. https://pubmed.ncbi.nlm.nih.gov/34466750/

2. Kulkarni, Rakesh, Kasani, Siti Khadijah, Tsai, Ching-Yen, Yu, Chen-Hsin Albert, Chang, Wen. 2023. FAM21 is critical for TLR2/CLEC4E-mediated dendritic cell function against Candida albicans. In Life science alliance, 6, . doi:10.26508/lsa.202201414. https://pubmed.ncbi.nlm.nih.gov/36717248/

3. Pahari, Susanta, Negi, Shikha, Aqdas, Mohammad, Schlesinger, Larry S, Agrewala, Javed N. 2019. Induction of autophagy through CLEC4E in combination with TLR4: an innovative strategy to restrict the survival of Mycobacterium tuberculosis. In Autophagy, 16, 1021-1043. doi:10.1080/15548627.2019.1658436. https://pubmed.ncbi.nlm.nih.gov/31462144/

4. Robles-Vera, Iñaki, Jarit-Cabanillas, Aitor, Brandi, Paola, Iborra, Salvador, Sancho, David. 2025. Microbiota translocation following intestinal barrier disruption promotes Mincle-mediated training of myeloid progenitors in the bone marrow. In Immunity, 58, 381-396.e9. doi:10.1016/j.immuni.2024.12.012. https://pubmed.ncbi.nlm.nih.gov/39848243/