Metrn-flox Mouse

Metrn, also known as meteorin, is a neurotrophin mainly expressed in the central nervous system, where it regulates glial cell differentiation and promotes axonal elongation [4]. Its homologous protein, METRNL, is associated with various metabolic regulatory pathways such as those related to lipid-induced inflammation, insulin resistance, and fatty acid oxidation through AMP-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor δ (PPARδ)-dependent pathways [3].

In colorectal cancer, METRN is overexpressed, especially in advanced stages and in the MSI (dMMR) subtype, often with BRAF mutations, and is associated with poor prognosis [1]. In glioma, the circular RNA hsa_circ_0037251 generated from METRN promotes cell proliferation, invasion, and migration by sponging miR-1229-3p and regulating mTOR expression [2]. In glioblastoma, low-dose radiation-induced exosomal circ-METRN enhances tumor progression and radioresistance via the miR-4709-3p/GRB14/PDGFRα pathway [5]. In the context of hematopoietic stem/progenitor cell (HSPC) mobilization, Metrn from hypoxic macrophages restrains HSPC mobilization, and macrophage-specific Metrn knockout increases HSPC mobilization [6]. In hyperalgesic priming in mouse models, Metrn is downregulated, and reversing its downregulation can reverse established hyperalgesic priming [7]. In preeclampsia, serum METRN levels are lower in early pregnancy in preeclamptic women compared to healthy pregnant women, and its measurement can assist in predicting preeclampsia [8].

In conclusion, Metrn plays diverse roles in multiple biological processes and disease conditions. Through various model-based research, it has been revealed that Metrn is involved in cancer progression, neural-related pain regulation, and pregnancy-associated disorders. The study of Metrn knockout or conditional knockout mouse models has provided valuable insights into its functions in these specific areas, contributing to a better understanding of the underlying mechanisms and potentially paving the way for new therapeutic strategies.