Bpifb1-flox Mouse

Bpifb1, also known as LPLUNC1, belongs to the BPI-fold-containing family. It is a natural immune protection molecule with bactericidal and osmotic enhancement protein domains, responding to external physical and chemical stimuli. It is involved in host defense, especially in airway mucociliary clearance (MCC), and may play roles in regulating chronic infections, inflammation, and tumor development [2].

In Bpifb1 knockout (KO) mice, effective MCC in vivo was diminished without defects in epithelial ion transport or ciliary beat frequency. Loss of Bpifb1 altered the biophysical and biochemical properties of mucus associated with impaired MCC, indicating its importance in the mucociliary apparatus and mucus protein network [1].

In nasopharyngeal carcinoma (NPC), Bpifb1 is downregulated. Overexpression of Bpifb1 promotes apoptosis, inhibits proliferation, migration, invasion, vasculogenic mimicry, and radioresistance in NPC cells through various mechanisms, such as regulating the MEK/ERK, JNK/AP1 signaling pathways, and interacting with proteins like VTN and VIM [3,5,6,7].

In hormone-receptor-positive breast cancer, high Bpifb1 expression is associated with lymph node metastasis, as it promotes metastasis by inducing macrophage M2-like polarization [4].

In cystic fibrosis (CF) lung disease, Bpifb1 is upregulated in human and mouse lungs [8].

In non-obese diabetic (NOD) mice, Bpifb1 mRNA is upregulated in parotid acinar cells, potentially predicting disease traits before autoimmunity onset [9]. Also, autoantibodies to Bpifb1 are associated with interstitial lung disease (ILD) in autoimmune polyglandular syndrome type 1 (APS1) and other ILD patients [10].

In conclusion, Bpifb1 plays crucial roles in multiple biological processes and diseases. The use of Bpifb1 KO mouse models has been instrumental in revealing its functions in airway MCC, tumor development in NPC and breast cancer, as well as its association with CF lung disease, potential disease prediction in NOD mice, and ILD. These findings enhance our understanding of Bpifb1's biological functions and its implications in disease mechanisms.