Deletion of seventeen amino acids at the C-terminal end of aquaporin 0 causes distortion aberration and cataract in the lenses of AQP0 ^ΔC/ΔC mice

PURPOSE. Investigate the effects of the absence of 17 amino acids at the C-terminal end of Aquaporin 0 (AQP0) on lens transparency, focusing property, and homeostasis. METHODS. A knockin (KI) mouse model (AQP0 ^DC/DC ) was developed to express AQP0 only as the end-cleaved form in the lens. For this, AQP0 was genetically engineered as C-terminally end-cleaved with amino acids 1 to 246, instead of the full length 1 to 263 of the wild type (WT). After verifying the KI integration into the genome and its expression, the mouse model was bred for several generations. AQP0 KI homozygous (AQP0 ^DC/DC ) and heterozygous (AQP0 ^+/DC ) lenses were imaged and analyzed at different developmental stages for transparency. Correspondingly, aberrations in the lens were characterized using the standard metal grid focusing method. Data were compared with age-matched WT, AQP0 knockout (AQP0 ^/ ), and AQP0 heterozygous (AQP0 ^+/ ) lenses. RESULTS. AQP0 ^DC/DC lenses were transparent throughout the embryonic development and until postnatal day 15 (P15) in contrast to age-matched AQP0 ^/ lenses, which developed cataract at embryonic stage itself. However, there was distortion aberration in AQP0 ^DC/DC lens at P5; after P15, cataract began to develop and progressed faster surpassing that of age-matched AQP0 ^/ lenses. AQP0 ^+/DC lenses were transparent even at the age of 1 year in contrast to AQP0 ^+/ lenses; however, there was distortion aberration starting at P15. CONCLUSIONS. A specific distribution profile of intact and end-cleaved AQP0 from the outer cortex to the inner nucleus is required in the lens for establishing refractive index gradient to enable proper focusing without aberrations and for maintaining transparency.