PTEN hamartoma syndrome (PHTS) is a diverse syndrome that develops as the result of mutations in the gene encoding the tumor suppressor PTEN. Cataract formation is common in PHTS patients; however, it is not clear if cataract onset is directly a result of PTEN loss or a secondary effect. Caterina Sellitto and colleagues at Stony Brook University generated a mouse line with lens-specific deletion of Pten to evaluate the contribution of PTEN to cataract development. Lenses from mice lacking PTEN exhibited increased hydrostatic pressure and intracellular sodium concentrations, which led to swelling, cataract, and eye rupture. The authors determined that AKT activation was increased in the lenses of these mice, and pharmacological inhibition of AKT reduced lens pressure. This study demonstrates that PTEN directly regulates lens ion transport via AKT and provides an animal model to investigate PHTS-associated cataract development. The accompanying image shows a WT mouse (top) and a mouse with lens-specific Pten deletion (bottom) at 24 weeks. Cataracts are clearly visible in the mutant animal.
Mutations in the human phosphatase and tensin homolog (
Caterina Sellitto, Leping Li, Junyuan Gao, Michael L. Robinson, Richard Z. Lin, Richard T. Mathias, Thomas W. White