Physiological and pathological impact of AQP1 knockout in mice

Abstract

Aquaporin 1 (AQP1) is a glycoprotein responsible for water passive transport quickly across biological membrane. Here, we reviewed the structural and functional impacts of AQP1 knockout (AQP1-KO) in animal or cell culture models. AQP1 gene deletion can cause a large number of abnormalities including the disturbance in epithelial fluid secretion, polyhydramnios, deficiency of urinary concentrating function, and impairment of pain perception. AQP1-KO mice also displayed aberrations of cardiovascular, gastrointestinal and hepatobiliary, and kidney functions as well as placenta and embryo development. Moreover, AQP1-KO perturbed tumor angiogenesis and led to reduced brain injury upon trauma. On the cellular level, AQP1-KO caused neuroinflammation, aberrant cell proliferation and migration, and macrophages infiltration. Mechanistic studies confirmed that AQP1 gene products regulate the secretory function and participated in balancing the osmotic water flux across the peritoneal membrane. The available data indicated that AQP1 might serve as a potential target for developing novel therapeutic approaches against diverse human diseases.

Keywords: Aquaporin 1; Knockout; Pathological Change; Physiological Change.

Figure 1. Physiological and pathological impact of AQP1-KO on organs and system

In AQP1-KO animal models or their cell culture models, AQP1 deletion was associated with defective urinary concentrating ability, polyhydramnios, cardiovascular homeostasis disorder, accelerating cataract formation, abnormalities in gastrointestinal and hepatobiliary function, neuroinflammation and protect in a model of brain trauma, reduced epithelial fluid secretion and impaired tumor angiogenesis and cell migration, and participating in the osmotic water flux across the peritoneal membrane.

Figure 2. AQP1-KO mice cannot generate a hypertonic medullary interstitium by countercurrent multiplication

AQP1-KO mice have suffered an 8-fold reduction in water permeability in proximal tubule membrane vesicles and driven fluid reabsorption from the lumen and luminal hypotonicity greater in the proximal tubules, resulting in disability to concentrate urine.