Multiple genetic loci modify risk for retinoblastoma in transgenic mice

Citation
Ae. Griep et al., Multiple genetic loci modify risk for retinoblastoma in transgenic mice, INV OPHTH V, 39(13), 1998, pp. 2723-2732
Citations number
53
Categorie Soggetti
da verificare
Journal title
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
ISSN journal
01460404 → ACNP
Volume
39
Issue
13
Year of publication
1998
Pages
2723 - 2732
Database
ISI
SICI code
0146-0404(199812)39:13<2723:MGLMRF>2.0.ZU;2-G
Abstract
PURPOSE. Forty percent of cases of retinoblastoma, a childhood malignancy o f the retina, are linked to the inheritance of a mutant allele of the retin oblastoma susceptibility gene Rb1. Tumor penetrance varies among carriers i n different family pedigrees, indicating that other genetic factors may mod ify risk for occurrence of retinoblastoma. This study was undertaken to det ermine whether multiple genetic loci modify the risk for retinoblastoma in mice. METHODS. A line of alpha AcryHPV16E6/E7 transgenic mice expressing the huma n 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 alpha Acry-HPV16E6/E7 tr ansgene was maintained on the FVB background, but tumors arose with high fr equency on C57BL/6 x FVB and C3H X FVB F-1 hybrid backgrounds. The incidenc e of retinoblastoma in the LH beta-TAG transgenic mice, which express simia n virus 40 large tumor antigen (SV40 T-ag), was also influenced by the FVB and C57BL/6 backgrounds. Resistance of the alpha Acry-HPV16E6/E7 FVB mice t o retinoblastoma mapped in part to the retinal degeneration (rd) locus. How ever, multiple genetic experiments indicate that resistance to retinoblasto ma depends on additional loci in FVB mice. CONCLUSIONS. Multiple cellular genes can modify risk for retinoblastoma in mice.