Mir146-KO Mouse

Mir146, a microRNA, is involved in regulating immune response, inflammation, and cell differentiation. It functions in pathways such as the NF-κB signaling pathway, and plays a significant role in various biological processes including spermatogenesis, and in disease contexts like cancer and neurodegeneration [1,2]. Mouse models are valuable for studying its function.

In mice, Mir146 was found to modulate spermatogonial differentiation, a key step in spermatogenesis. Its levels were highly regulated during this process, with decreased levels in differentiating spermatogonia. Overexpression of Mir146 reduced levels of mediator complex subunit 1 (Med1) and the differentiation marker Kit, while its inhibition increased Kit levels, indicating its role in the retinoic acid-mediated spermatogonial differentiation [1]. In microglia, Presenilin 2 (PS2) was shown to influence Mir146 levels. PS2 knockout microglia had constitutively down-regulated Mir146, leading to increased levels of the miR146 target protein interleukin-1 receptor-associated kinase-1 and enhanced NFκB transcriptional activity, suggesting a role for PS2-regulated Mir146 in curbing microglial pro-inflammatory responses [2].

In summary, Mir146 plays essential roles in spermatogonial differentiation and microglial inflammatory regulation. Mouse models, especially the PS2 knockout model, have been crucial in revealing its role in neurodegenerative disease-related microglial dysregulation, highlighting its potential significance in understanding the mechanisms underlying neurodegenerative diseases [1,2].

References:

1. Huszar, Jessica M, Payne, Christopher J. 2013. MicroRNA 146 (Mir146) modulates spermatogonial differentiation by retinoic acid in mice. In Biology of reproduction, 88, 15. doi:10.1095/biolreprod.112.103747. https://pubmed.ncbi.nlm.nih.gov/23221399/

2. Jayadev, Suman, Case, Amanda, Alajajian, Betty, Möller, Thomas, Garden, Gwenn A. 2013. Presenilin 2 influences miR146 level and activity in microglia. In Journal of neurochemistry, 127, 592-9. doi:10.1111/jnc.12400. https://pubmed.ncbi.nlm.nih.gov/23952003/