Abstract
Abstract: :
Purpose: Retinoblastoma is the most common intraocular malignant tumor in childhood. In this study, we generated families of transgenic mice that provide excellent animal models of retinoblastoma. Methods: A modified Pax6 promoter was used to target expression of wild type SV40 T antigen to retinal cells at an early developmental stage. Microinjections were used to generate transgenic mice. Mice expressing SV40 T antigen were characterized by PCR screening, histological analysis and immunohistochemistry assays. Results: Three stable families (OVE1796, OVE1754 and OVE1794) have been generated. After postnatal day 14 (P14), eye tumors were seen in OVE1796 and OVE1754 mice. Without eye enucleation, transgenic mice from these two families usually die in two months due to rapid tumor growth. OVE1794 transgenic mice showed mild cataracts when they opened their eyes. After three months, transgenic mice from this line developed eye tumors with low–penetration. Ocular histology revealed that rosettes were formed in prenatal OVE1796 retinas. Expression of SV40 T antigen was detected in conjunctival, corneal and lens epithelial cells as well as different populations of retinal cells at prenatal and postnatal stages. Retinal cell proliferation was altered. Based upon staining with a phosphorylated histone H3 antibody, one of the earliest changes in the retinoblastomas is ectopic positioning of the mitotic apparatus, a heretofore un–recognized function of the Rb family members. Conclusions: Inactivation of the Rb family of proteins in embryonic mouse retinas induces retinoblatoma. These mouse models may be used for in vivo studies on novel strategies to treat retinoblatoma.
Keywords: retina • tumors • retinoblastoma