A predominant form of C-terminally end-cleaved AQP0 functions as an open water channel and an adhesion protein in AQP0 mouse lens.

The purpose of this investigation was to find out whether C-terminally end-cleaved aquaporin 0 (AQP0), that is present predominantly in the lens mature fiber cells of the WT, functions as a water channel and a cell-to-cell adhesion (CTCA) protein in a knockin (KI) mouse model (AQP0) that does not express intact AQP0. A genetically engineered KI mouse model, AQP0, expressing only end-cleaved AQP0 was developed. This model expresses 1-246 amino acids of AQP0, instead of the full length 1-263 amino acids. Lens transparency of postnatal day 10 (P10) was analyzed qualitatively by dark field imaging. WT, AQP0 and AQP0 lenses were transparent; AQP0 and AQP0 mouse lenses displayed loss of transparency. Lens fiber cell membrane vesicles (FCMVs) were prepared from wild type (WT), AQP0 heterozygous (AQP0), AQP0 knockout (AQP0), AQP0 and AQP0; water permeability (P) was measured using the osmotic shrinking method. CTCA assay was performed using adhesion-deficient L-cells and FCMVs prepared from the abovementioned genotypes. FCMVs of AQP0 and AQP0 showed a statistically significant reduction (P < 0.001) in P and CTCA compared to those of WT. AQP0 and AQP0 FCMVs exhibited no statistically significant alteration (P > 0.05) in P compared to those of WT. However, CTCA of AQP0 AQP0 FCMVs was significantly higher (P < 0.001) than that of WT FCMVs. Our experiments clearly show that C-terminally end-cleaved AQP0 can function both as a water channel and a CTCA molecule in the lens fiber cell membranes. Also, end-truncation plays an important role in increasing the CTCA between fiber cells.