Apoptosis or retinoblastoma: Alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53

Kimberly A. Howes, Nancy Ransom, David S. Papermaster, Jacques G.H. Lasudry, Daniel M. Albert, Jolene J. Windle

Research output: Contribution to journalArticle

279 Scopus citations

Abstract

A transgenic mouse model for retinoblastoma was produced previously by directing SV40 T antigen expression to retinal photoreceptor cells using the promoter of the interstitial retinol-binding protein (IRBP) gene. This gene becomes active prior to the terminal differentiation of photoreceptors. Because T antigen-transforming activity is attributable, at least in part, to the inactivation of the retinoblastoma (pRb) and p53 tumor suppressor proteins, we addressed the role of p53 in the development of retinoblastoma in mice. Transgenic mice expressing HPV-16 E7 under the control of the IRBP promoter were generated to inactivate pRb in photoreceptors while leaving p53 intact. Rather than developing retinoblastomas, the retinas of these mice degenerate due to photoreceptor cell death at a time in development when photoreceptors are normally undergoing terminal differentiation. The dying cells exhibit the histological and ultrastructural features of apoptosis and contain fragmented DNA. p53 is required for the induction of apoptosis in this model, because mice expressing E7 in a p53 nullizygous background develop retinal tumors instead of undergoing retinal degeneration.

Original languageEnglish (US)
Pages (from-to)1300-1310
Number of pages11
JournalGenes and Development
Volume8
Issue number11
DOIs
StatePublished - Jan 1 1994

Keywords

  • HPV E7
  • Retinoblastoma
  • apoptosis
  • p53
  • photoreceptors
  • transgenic mice

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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