C57BL/6JCya-Faf1^em1flox/Cya

Faf1, or Fas-associated factor 1, is an evolutionarily conserved protein with multiple protein-interaction domains. Initially recognized as part of the FAS death-inducing signaling complex, it is involved in diverse biological processes. Faf1 has been shown to be important in normal development, neuronal cell survival, and is also associated with pathways like apoptosis, NFκB activity, ubiquitination, and proteasomal degradation [2].

In terms of disease-related findings, in KO mice, Faf1 deficiency did not lead to pituitary lesions or differences in corticosterone secretion, despite the identification of potentially pathogenic Faf1 variants in Cushing's disease patients [1]. Faf1 knockout mice were more resistant to RNA virus infection, with Faf1 deficiency in myeloid cells enhancing innate signaling and reducing viral load and morbidity [3]. In a Parkinson's disease mouse model, targeting Faf1 with KM-819 restored autophagic flux for α-synuclein degradation [4]. In breast cancer, Faf1-knockout animals and various models revealed that Faf1 phosphorylation by AKT accumulates TGF-β type II receptor and drives breast cancer metastasis [5].

In conclusion, Faf1 plays crucial roles in multiple biological processes and disease conditions. Gene knockout mouse models have been instrumental in uncovering its functions in antiviral immunity, neurodegenerative diseases like Parkinson's, and cancers such as breast cancer and potentially pituitary tumors. Understanding Faf1's functions provides insights into disease mechanisms and potential therapeutic targets.