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Steven Bassnett, Yanrong Shi, Alicia De Maria, Jennifer King-Sitzes, Thomas Bennett, Alan Shiels; Latent Lens Phenotype in Mice Lacking Eph-receptor A2. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4774.
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© ARVO (1962-2015); The Authors (2016-present)
Variations in the gene coding for ephrin type-A receptor-2 (EphA2) have been associated with a cataract phenotype in humans and mice. Here we characterize the lens phenotype of Epha2 gene-targeted mice that do not develop obvious cataract.
Commercially available Epha2-targeted mice were characterized by standard PCR-amplification and sequencing techniques. Lenses were analyzed by immuno-blotting, bright-field microscopy, and confocal fluorescence microscopy techniques.
DNA/RNA amplification and sequencing confirmed that the Epha2 gene was disrupted in exon-5 resulting in several mutant transcripts consistent with a functional null at the protein level. Lens immunoblot analysis and confocal immunofluorescence microscopy localized Epha2 to plasma-membranes of the anterior epithelium and peripheral cortical fibers of wild-type but not null mice. Bright-field microscopy showed that Epha2-null lenses were smaller than wild-type and, while transparent, displayed a mild central refractive disturbance. Confocal fluorescence imaging of live Epha2-null lenses revealed at least four other features not observed in wild-type: (1) anterior and posterior Y-sutures were offset from the optical axis and composed of 1-5 asymmetric branches, (2) fiber cell nuclei at the lens equator appeared disorganized and were retained with age, (3) isolated fiber cells lacked characteristic undulation along their anterior-posterior axis, and (4) membranous dome-like structures protruded from the basal surface of the anterior epithelium into the surrounding capsule.
Homozygous loss of Epha2 affects lens growth and optical quality, but is not necessarily sufficient to cause cataract in mice. Absence of Epha2 is also associated with mis-targeting of fiber cells to the suture regions, abnormal fiber cell shape and denucleation, and aberrant basal protrusions from the anterior epithelium. These data point to a key role for Epha2-dependent cell signaling in normal lens development.
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