Prss8-KO Mouse

Prss8, also known as prostasin or CAP1 (channel-activating protease-1), is a glycosylphosphatidylinositol-anchored serine protease. It is ubiquitously expressed in multiple tissues like kidney, prostate, skin, etc. Prss8 is a confirmed activator of the epithelial sodium channel ENaC and has been linked to pathways such as Wnt/β -catenin, epithelial-mesenchymal transition, and stem cell signaling pathways, playing important roles in physiological and pathological processes [2,3]. Genetic models, especially knockout mouse models, have been crucial in studying its functions.

A conditional knockout Prss8fl/fl, p-Villin-Cre+ mouse model showed that genetic deficiency of Prss8 led to spontaneous colitis, an inflamed rectum at an early age, and intestinal tumors at a late age. This was due to increased intestinal cell proliferation and migration but decreased cell differentiation. In contrast, increased PRSS8 expression inhibited cancer cell growth and metastasis in nude mice and various cancer-related processes in vitro [1]. Kidney-specific Prss8 knockout mice maintained ENaC-mediated sodium balance through an aldosterone-independent pathway, indicating that the catalytic activity of Prss8 is dispensable for proteolytic ENaC activation [2].

In conclusion, Prss8 plays essential roles in maintaining physiological functions such as sodium balance and in suppressing carcinogenesis, especially in colorectal cancer as shown by the knockout mouse models. These models have significantly contributed to understanding the role of Prss8 in specific disease areas, highlighting its potential as a therapeutic target and biomarker.