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I. Ivanovic, M. R. Al-Ubaidi; Developmental p53 Down-Regulation - Is It a Preventive Approach to Retinal Degeneration?. Invest. Ophthalmol. Vis. Sci. 2007;48(13):599.
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To evaluate the significance of p53 down-regulation during retinal development.
Developmental pattern of expression of p53 and either regulator or target genes of p53 were analyzed by real time PCR (qRT-PCR). Transgenic mice that express p53 in the adult rod and cone photoreceptors were developed using a PCR-generated p53 vector whereby p53 is driven by the human IRBP promoter. Western analysis was used to determine the expression pattern of p53. Immunohistochemical and histologic analyses and electroretinography (ERG) recordings were used to assess cellular localization of transgenic p53, and structural and functional phenotypes, respectively.
qRT-PCR data demonstrated the down-regulation of the p53 transcript in the retina while Mdm2 mRNA levels are kept relatively steady throughout development. Four HIP (human IRBP-p53) transgenic lines, with varying levels of p53 expression, were generated. p53 was localized in the photoreceptor’s inner segments and perinuclear space. Histologic examination showed loss of photoreceptor nuclei at as early as 90 days of age. ERG recordings, with reduced scotopic and photopic responses, reflected the observed structural changes. However, the functional deficit is more pronounced in cones than in rods at any age tested.
During vertebrate retinal development, p53 expression is down-regulated. Transgenic expression of p53 in the murine retina compromises function and structure of the photoreceptors affecting predominantly cone cells. Studying the underlying mechanisms of the p53-induced degenerative retinal phenotype will provide a better understanding of p53 regulation and the correlation between p53 expression and retinal degenerations.
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