Multiple genetic loci modify risk for retinoblastoma in transgenic mice

Anne E. Griep, Jeff Krawcek, Denis Lee, Amy Liem, Daniel M. Albert, Rey Carabeo, Norman Drinkwater, Maureen McCall, Carol Sattler, Jacques G.H. Lasudry, Paul F. Lambert

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29 Scopus citations

Abstract

PURPOSE. Forty percent of cases of retinoblastoma, a childhood malignancy of the retina, are linked to the inheritance of a mutant allele of the retinoblastoma susceptibility gene Rb1. Tumor penetrance varies among carriers in different family pedigrees; indicating that other genetic factors may modify risk for occurrence of retinoblastoma. This study was undertaken to determine whether multiple genetic loci modify the risk for retinoblastoma in mice. METHODS. A line of αAcry-HPV16E6/E7 transgenic mice expressing the human papillomavirus type 16 E6 and E7 oncogenes (HPV-16 E6 and E7) ectopically in the retina was characterized. E6 and E7 proteins bind to and inactivate the cellular tumor suppressor proteins p53 and Rb, respectively. RESULTS. Retinoblastomas developed rarely when the αAcry-HPV16E6/E7 transgene was maintained on the FVB background, but tumors arose with high frequency on C57BL/6 X FVB and C3H X FVB F1 hybrid backgrounds. The incidence of retinoblastoma in the LHβ-TAG transgenic mice, which express simian virus 40 large tumor antigen (SV40 T-ag), was also influenced by the FVB and C57BL/6 backgrounds. Resistance of the αAcry-HPV16E6/E7 FVB mice to retinoblastoma mapped in part to the retinal degeneration (rd) locus. However, multiple genetic experiments indicate that resistance to retinoblastoma depends on additional loci in FVB mice. CONCLUSIONS. Multiple cellular genes can modify risk for retinoblastoma in mice.

Original languageEnglish (US)
Pages (from-to)2723-2732
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume39
Issue number13
StatePublished - Dec 1 1998

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ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Griep, A. E., Krawcek, J., Lee, D., Liem, A., Albert, D. M., Carabeo, R., Drinkwater, N., McCall, M., Sattler, C., Lasudry, J. G. H., & Lambert, P. F. (1998). Multiple genetic loci modify risk for retinoblastoma in transgenic mice. Investigative Ophthalmology and Visual Science, 39(13), 2723-2732.