Griep A E, Krawcek J, Lee D, Liem A, Albert D M, Carabeo R, Drinkwater N, McCall M, Sattler C, Lasudry J G, Lambert P F
Department of Anatomy, University of Wisconsin Medical School, Madison 53706, USA.
Invest Ophthalmol Vis Sci. 1998 Dec;39(13):2723-32.
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.
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.
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.
Multiple cellular genes can modify risk for retinoblastoma in mice.
视网膜母细胞瘤是一种儿童期视网膜恶性肿瘤，40%的病例与视网膜母细胞瘤易感基因Rb1的突变等位基因遗传有关。肿瘤外显率在不同家族谱系的携带者中有所不同，这表明其他遗传因素可能会改变视网膜母细胞瘤发生的风险。本研究旨在确定多个基因位点是否会改变小鼠患视网膜母细胞瘤的风险。
对一组αAcry-HPV16E6/E7转基因小鼠进行了表征，该小鼠在视网膜中异位表达人乳头瘤病毒16型E6和E7癌基因（HPV-16 E6和E7）。E6和E7蛋白分别与细胞肿瘤抑制蛋白p53和Rb结合并使其失活。
当αAcry-HPV16E6/E7转基因保持在FVB背景上时，视网膜母细胞瘤很少发生，但在C57BL/6×FVB和C3H×FVB F1杂交背景上肿瘤高发。表达猿猴病毒40大肿瘤抗原（SV40 T-ag）的LHbeta-TAG转基因小鼠中视网膜母细胞瘤的发生率也受FVB和C57BL/6背景的影响。αAcry-HPV16E6/E7 FVB小鼠对视网膜母细胞瘤的抗性部分定位于视网膜变性（rd）位点。然而，多项遗传学实验表明，FVB小鼠对视网膜母细胞瘤的抗性取决于其他位点。
多个细胞基因可改变小鼠患视网膜母细胞瘤的风险。
