Pattern of expression of p53, its family members, and regulators during early ocular development and in the post-mitotic retina

Invest Ophthalmol Vis Sci. 2012 Jul 20;53(8):4821-31. doi: 10.1167/iovs.11-8681.

Abstract

Purpose: Because of its role in cell cycle regulation and apoptosis, p53 may be involved in maintaining the post-mitotic state of the adult eye. To shed light on the role of p53 in retinal development and maintenance, this study investigated the pattern of expression of p53, its family members, and its regulators during the development of the mouse eye.

Methods: Relative quantitative real-time PCR (qRT-PCR) was used to determine the steady-state levels of target transcripts in RNA extracted from wild-type mouse whole eyes or retinas between embryonic day (E) 15 and post-natal day (P) 30. Immunoblotting was used to compare the steady-state levels of the protein to that of the transcript.

Results: Transcript and protein levels for p53 in the eye were highest at E17 and E18, respectively. However, both p53 transcript and protein levels dropped precipitously thereafter, and no protein was detected on immunoblots after P3. Expression patterns of p63, p73, Mdm2, Mdm4, and Yy1 did not follow that of p53. Immunohistochemistry analysis of the developing eye showed that both p53 and Mdm2 are abundantly expressed at E18 in all layers of the retinal neuroblast.

Conclusions: Downregulation of p53 in the post-mitotic retina suggests that, although p53 may be involved in ocular and retinal development, it may play a minimal role in healthy adult retinal function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Genes, p53 / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / metabolism
  • Phosphoproteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Real-Time Polymerase Chain Reaction
  • Retina / embryology
  • Retina / growth & development
  • Retina / metabolism*
  • Trans-Activators / metabolism
  • Tumor Protein p73
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • YY1 Transcription Factor / metabolism

Substances

  • DNA-Binding Proteins
  • Mdm4 protein, mouse
  • Nuclear Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Trp63 protein, mouse
  • Trp73 protein, mouse
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • YY1 Transcription Factor
  • Yy1 protein, mouse
  • Proto-Oncogene Proteins c-mdm2
  • Ubiquitin-Protein Ligases