Amfr-KO Mouse

Amfr, also known as autocrine motility factor receptor, is an endoplasmic reticulum-resident E3 ubiquitin ligase. It plays crucial roles in multiple biological processes, including the regulation of ubiquitination-related pathways, which are involved in various cellular functions such as immune response, cell-cell communication, and ER-phagy [1,2,3,6]. Genetic models, like gene knockout (KO) mouse models, are valuable for studying its functions.

In allergic asthma, Amfr deficiency in alveolar macrophages significantly decreased allergy-induced T helper 2 (Th2) and eosinophilic inflammation, with less granulocyte-macrophage colony-stimulating factor (GM-CSF) production [1]. In Zika virus infection, a recombinant ZIKV mutant lacking AMFR-mediated NS2A ubiquitination, which subverts ER-phagy, exhibited attenuation in ZIKV-induced microcephalic phenotypes in human brain organoids and less efficient replication in mouse models [2]. In intracellular Staphylococcus aureus infection, deletion of Amfr in macrophages could potentially prevent invasive staphylococci-mediated pneumonia by disrupting the AMFR-TAB3 signalling cascade [3]. In pulmonary fibrosis, deletion of Amfr in fibroblasts impaired their activation triggered by the CCL1-AMFR-SPRY1 pathway [4]. In a zebrafish model of autosomal recessive spastic paraplegia caused by AMFR dysfunction, statin treatment improved motor neuron-related phenotypes [5]. In influenza virus-infected A549 cells, knockdown of AMFR inhibited HMGCR ubiquitination and innate immunity activation [7].

In conclusion, Amfr is essential in regulating immune responses, viral infections, fibroblast activation, and lipid metabolism. KO or conditional knockout (CKO) mouse models and other in vivo studies have revealed its significance in diseases such as allergic asthma, flavivirus-induced pathologies, staphylococcal pneumonia, pulmonary fibrosis, and spastic paraplegia. Understanding Amfr's functions provides potential therapeutic targets for these diseases.