Multiple genetic loci modify risk for retinoblastoma in transgenic mice.
OBJECTIVE
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.
Griep
A E
AE
Department of Anatomy, University of Wisconsin Medical School, Madison 53706, USA.
Krawcek
J
J
Lee
D
D
Liem
A
A
Albert
D M
DM
Carabeo
R
R
Drinkwater
N
N
McCall
M
M
Sattler
C
C
Lasudry
J G
JG
Lambert
P F
PF
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins; D005260:Female; D005838:Genotype; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D012160:Retina / Q000473:pathology* / Q000821:virology; D019572:Retinal Neoplasms / Q000235:genetics* / Q000473:pathology; D012175:Retinoblastoma / Q000235:genetics* / Q000473:pathology; D016160:Retinoblastoma Protein / Q000235:genetics; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D000952:Antigens, Polyomavirus Transforming; D017931:DNA Primers; D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C059731:oncogene protein E7, Human papillomavirus type 16