Browsing by Author "Borders, Nathaniel"
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Item FUNCTIONAL CHARACTERIZATION OF RNA BINDING PROTEIN CAPRIN2 IN MOUSE EYE DEVELOPMENT(University of Delaware, 2017-05) Borders, NathanielThe iSyTE bioinformatics tool developed by the Lachke laboratory previously identified that a novel RNA binding protein (RBP) and RNA granule component, Caprin2, is enriched in the mouse lens at the early embryonic (E) day 10.5 and later stages. It was demonstrated that Caprin2 mRNA and protein were localized to lens fiber cells, supporting the hypothesis that it has potential function in lens development. It was also demonstrated that a lens-specific conditional mouse knockout of Caprin2 (Caprin2cKO/cKO) resulted in nuclear fiber cell compaction and a persistent lenti-corneal stalk. However, the lenti-corneal stalk phenotype was only observed at 8% penetrance in Caprin2cKO/cKO mouse eyes. We hypothesized that one of the reasons for the low penetrance of this ocular defect may result from residual Caprin2 protein present at E12.5 in the mutant mice. Therefore, Caprin2 germline (Caprin2-/-) deletion knockout mouse mutants that would lack Caprin2 protein earlier in embryogenesis were generated to test this hypothesis. Phenotypic characterization involving histology and scanning electron microscopy did not reveal any obvious ocular defects in Caprin2-/- mice. Further analyses revealed that Caprin1, a paralogous RNA binding protein, is upregulated in the Caprin2-/- lens. Interestingly, while Caprin1 protein levels were elevated, its mRNA was not found to be significantly different in Caprin2-/- lenses at E14.5, suggesting a potential post-transcriptional mechanism as the basis of the Caprin1 up-regulation in the mutant lens. These findings suggest that removal of Caprin2 earlier in embryogenesis causes the up-regulation of Caprin1 that may result in redundancy and “rescue” of the ocular defects observed in Caprin2cKO/cKO mouse eyes. Therefore, Caprin1 and Caprin2 double knockout mouse mutants may need to be generated to test this hypothesis in the future.