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P. McGannon, Y. Miyazaki, P. Gupta, E.I. Traboulsi, C. Colmenares; Expression of PAX6 and betaIII Tubulin in Fetal Eyes of Ski–Deficient Mice With PHPV and Peters Anomaly . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3530.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Persistent hyperplastic primary vitreous (PHPV) is an uncommon developmental ocular malformation often associated with additional anterior segment and retinal abnormalities. The eyes of mice lacking the Ski proto–oncogene display several of the characteristics of PHPV in addition to what resembles Peter's anomaly. We review the spectrum of ocular malformations in fetal Ski–/– mice and we report on the expression of Pax6 and B= tubulin in these eyes. Methods: Morphologic and histologic analyses of Ski–/– mice were used to document ocular abnormalities and compared to eye morphology of normal, +/– and +/+ littermates. Immunohistochemical studies were used to examine the expression of Pax6 as a marker of eye development, and of B=tubulin as a neural cell marker to determine the cellular origin of abnormal vitreal tissue. Assays for apoptosis were used to test the hypothesis that alterations in programmed cell death underlie the observed abnormalities. Mouse eyes were harvested between E16 and E18. Results: The incidence of PHPV and microphthalmia in Ski–deficient fetuses was 100%. Other abnormalities included some degree of anterior segment and lens dysgenesis in all animals, retinal folds (78%), chorioretinal coloboma (78%), and Peter's anomaly (44%). The severity of these phenotypes was variable even in a highly homogeneous genetic background. PHPV was characterized by variable amounts of retrolental fibrous tissue. This mesenchymal tissue did not express the neural marker B=tubulin, and occasionally contained pigmented cell nodules. Pax6 expression was significantly reduced in the retina of 3 mutant mice as compared to normal littermates. Conclusions: Normal ocular development requires the function of the Ski proto–oncogene, and mice lacking Ski have many features associated with PHPV and Peter's anomaly in humans. Defects in Ski–deficient mice closely resemble those described in animals lacking several of the retinoic acid receptor genes, or in animals exposed to excess retinoic acid during gestation. Ski has been shown to repress transcription induced by retinoic acid signaling, and may affect ocular development by regulating RA signaling. This may account for the reduced expression of Pax6 that we observed in Ski–deficient animals. Reduced Pax6 activity may also be responsible for the Peter's phenotype as described in humans.
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