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D-J Oh, A Cvekl, MK Duncan; Expression of Etv6 In Murine Lens . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2330.
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Purpose: Pax6 is required for induction, growth and maintenance of the lens. Pax6(5a) transgenic mice have drastic alterations in lens fiber cell morphology, resulting in cataract. Etv6 was identified by cDNA microarrays as one of the abnormally expressed genes in transgenic lenses over-expressing Pax6(5a). Etv6, an Ets-variant gene, is a nuclear phosphoprotein essential for normal development of the hematopoietic system, where it acts as a transcriptional repressor. In order to explore the relationship between Pax6 and Etv6, we investigated the developmental expression patterns of Etv6 in normal and Pax6(5a)-over-expressing mouse lenses. In addition, the expression pattern of Ets-2, another member of the Ets family of transcription factors, was investigated in mouse lenses over-expressing Pax6(5a) in order to be compared with that of Etv6. Methods: The expression pattern of Etv6 was assessed by immunohistochemistry in embryonic and postnatal mouse lenses. The expression patterns of Etv6 and Ets-2 in Pax6(5a)-transgenic and normal lenses were determined by western blotting and immunohistochemistry. Results: The cellular distribution of Etv6 during mouse lens development was determined. In the lens placode, lens pit and lens vesicle of E9.5, E10.5 and E11.5 embryos, Etv6 was found in the plasma membrane of all lens cells. However, at E12.5, E14.5 and E16.5, Etv6 was found in the nuclei of both lens epithelial and fiber cells and a relatively small amount of Etv6 was detected in the cytoplasm of epithelial cells. In the postnatal lenses of newborn, young adult and adult mice, Etv6 had the same distribution pattern as at E12.5, E14.5 and E16.5, but the expression of Etv6 was greatly reduced in the cytoplasm of epithelial cells. In the Pax6(5a) over-expressing adult lens, the expression level of Etv6 was decreased, whereas the expression level of Ets-2 was increased. Conclusion: Etv6 is expressed in both lens fiber cells where it is found in the nuclei, and lens epithelial cells where it is found in both the cytoplasm and nuclei, but is more concentrated in the nuclei. The results also showed that Pax6(5a) may cause down-regulation of Etv6 expression, but cause up-regulation of Ets-2 expression. Further study is needed to explore the functional relationship among Etv6, Ets-2 and Pax6 during lens differentiation.
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