Biochemical and biomechanical characteristics of dystrophin-deficient mdx(3cv) mouse lens

The molecular and cellular basis for cataract development in mice lacking dystrophin, a scaffolding protein that links the cytoskeleton to the extracellular matrix, is poorly understood. In this study, we characterized lenses derived from the dystrophin-deficient mdx(3cv) mouse model. Expression of Dp71, a predominant isoform of dystrophin in the lens, was induced during lens fiber cell differentiation. Dp71 was found to co-distribute with dystroglycan, connexin-50 and 46, aquaporin-0, and NrCAM as a large cluster at the center of long arms of the hexagonal fibers. Although mdx(3cv) mouse lenses exhibited dramatically reduced levels of Dp71, only older lenses revealed punctate nuclear opacities compared to littermate wild type (WT) lenses. The levels of dystroglycan, syntrophin, and dystrobrevin which comprise the dystrophin-associated protein complex (DAPC), and NrCAM, connexin-50, and aquaporin-0, were significantly lower in the lens membrane fraction of adult mdx(3cv) mice compared to WT mice. Additionally, decreases were observed in myosin light chain phosphorylation and lens stiffness together with a significant elevation in the levels of utrophin, a functional homolog of dystrophin in mdx(3cv )mouse lenses compared to WT lenses. The levels of perlecan and laminin (ligands of a-dystroglycan) remained normal in dystrophin-deficient lens fibers. Taken together, although mdx(3cv) mouse lenses exhibit only minor defects in lens clarity possibly due to a compensatory increase in utrophin, the noted disruptions of DAPC, stability, and organization of membrane integral proteins of fibers, and stiffness of mdx(3cv) lenses reveal the importance of dystrophin and DAPC in maintaining lens clarity and function.

Automated summary

This study characterized lenses derived from dystrophin-deficient mice and found changes in the distribution of Dp71 and other integral membrane proteins, resulting in decreased lens stiffness. The reductions in DAPC levels in dystrophin-deficient lenses indicate the importance of dystrophin in maintaining lens clarity and function.