| First Author | Sellitto C | Year | 2016 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 57 |
| Issue | 7 | Pages | 3145-51 |
| PubMed ID | 27304846 | Mgi Jnum | J:257615 |
| Mgi Id | MGI:6112381 | Doi | 10.1167/iovs.16-19607 |
| Citation | Sellitto C, et al. (2016) The Phosphoinosotide 3-Kinase Catalytic Subunit p110alpha is Required for Normal Lens Growth. Invest Ophthalmol Vis Sci 57(7):3145-51 |
| abstractText | PURPOSE: Signal transduction pathways influence lens growth, but little is known about the role(s) of the class 1A phosphoinositide 3-kinases (PI3Ks). To further investigate how signaling regulates lens growth, we generated and characterized mice in which the p110alpha and p110beta catalytic subunits of PI3K were conditionally deleted in the mouse lens. METHODS: Floxed alleles of the catalytic subunits of PI3K were conditionally deleted in the lens by using MLR10-cre transgenic mice. Lenses of age-matched animals were dissected and photographed. Postnatal lenses were fixed, paraffin embedded, sectioned, and stained with hematoxylin-eosin. Cell proliferation was quantified by labeling S-phase cells in intact lenses with 5-ethynyl-2''-deoxyuridine. Protein kinase B (AKT) activation was examined by Western blotting. RESULTS: Lens-specific deletion of p110alpha resulted in a significant reduction of eye and lens size, without compromising lens clarity. Conditional knockout of p110beta had no effect on lens size or clarity, and deletion of both the p110alpha and p110beta subunits resulted in a phenotype that resembled the p110alpha single-knockout phenotype. Levels of activated AKT were decreased more in p110alpha- than in p110beta-deficient lenses. A significant reduction in proliferating cells in the germinative zone was observed on postnatal day 0 in p110alpha knockout mice, which was temporally correlated with decreased lens volume. CONCLUSIONS: These data suggest that the class 1A PI3K signaling pathway plays an important role in the regulation of lens size by influencing the extent and spatial location of cell proliferation in the perinatal period. |
