Multiple genetic loci modify risk for retinoblastoma in transgenic mice.

Anne Griep // Publications // Dec 18 1998

PubMed ID: 9856783

Author(s): Griep AE, Krawcek J, Lee D, Liem A, Albert DM, Carabeo R, Drinkwater N, McCall M, Sattler C, Lasudry JG, Lambert PF. Multiple genetic loci modify risk for retinoblastoma in transgenic mice. Invest Ophthalmol Vis Sci. 1998 Dec;39(13):2723-32.

Journal: Investigative Ophthalmology & Visual Science, Volume 39, Issue 13, Dec 1998

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 alphaAcry-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 alphaAcry-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 LHbeta-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 alphaAcry-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.