Wdfy1-flox Mouse

Wdfy1, the WD repeat and FYVE domain containing 1 gene, encodes a 410-amino acid protein with 97.8% amino acid sequence identity to the human WDFY1 protein [1]. It is involved in crucial biological processes such as the TLR3/4 signaling pathway in the innate immune system, where it mediates the recruitment of TRIF to TLR3 and TLR4, potentiating the activation of NF-κB, IRF3, and production of type I interferons and inflammatory cytokines [3]. It also plays a role in lysophagy initiation as part of the CUL4A-DDB1-WDFY1 E3 ubiquitin ligase complex [4].

Global Wdfy1 knockout (KO) male mice show normal growth, development, and fertility, indicating that WDFY1 is dispensable for mouse spermatogenesis and male fertility [1]. Wdfy1-deficient mice display impaired Tlr3-mediated immune responses in vivo [2]. In a cGVHD mouse model, WDFY1-expressing follicular dendritic cells are critical for lupus development as Wdfy1 knockout impairs the normal functioning of FDCs, resulting in reduced auto-Ab response to cGVHD [5].

In conclusion, Wdfy1 has essential functions in the innate immune response and lysophagy. The gene knockout mouse models have revealed its non-essential role in spermatogenesis and male fertility, as well as its importance in certain immune-related disease conditions like Tlr3-mediated immune responses and lupus development.