| First Author | Varadaraj K | Year | 2019 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 60 |
| Issue | 4 | Pages | 858-867 |
| PubMed ID | 30821811 | Mgi Jnum | J:272334 |
| Mgi Id | MGI:6281532 | Doi | 10.1167/iovs.18-26378 |
| Citation | Varadaraj K, et al. (2019) Deletion of Seventeen Amino Acids at the C-Terminal End of Aquaporin 0 Causes Distortion Aberration and Cataract in the Lenses of AQP0DeltaC/DeltaC Mice. Invest Ophthalmol Vis Sci 60(4):858-867 |
| abstractText | 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 (AQP0DeltaC/DeltaC) 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 (AQP0DeltaC/DeltaC) and heterozygous (AQP0+/DeltaC) 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: AQP0DeltaC/DeltaC 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 AQP0DeltaC/DeltaC lens at P5; after P15, cataract began to develop and progressed faster surpassing that of age-matched AQP0-/- lenses. AQP0+/DeltaC 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. |
