EXPRESSION OF THE RAST24 ONCOGENE IN THE CILIARY BODY PIGMENT-EPITHELIUM AND RETINAL-PIGMENT EPITHELIUM RESULTS IN HYPERPLASIA, ADENOMA, AND ADENOCARCINOMA

We examined eye lesions in five lines of transgenic mice carrying the human rasT24 oncogene driven by the type I gamma glutamyl transferase (gammaGT) promoter. In three lines, hyperplasia developed as early as 11.5 days postconception in the outer neuroectodermal layer, which giv es rise to ciliary body and retinal pigment epithelium. At birth, the eyes from many animals contained adenomas, and by day 27, mice develop ed invasive adenocarcinomas originating in the region of the ciliary b ody. Microphthalmia, cataracts, and chronic nongranulomatous inflammat ion involving the anterior and/or posterior segments of the eye were a lso found gammaGT is detectable histochemically as early as 11.5 gesta tional days in the outer neuroectodermal layer and after birth is more abundant in the ciliary body than in the retinal pigment epithelium U sing a reverse transcriptase-polymerase chain reaction, we found that type I (but not types II or III) gammaGT RNA is made by the mouse eye, the gammaGT(I)rasT24 transgene transcription product was detected in the eyes of all five transgenic lines. The sequential progression of h yperplasia to invasive neoplasms in the ciliary body in response to ga mma GT(I) rasT24 expression differs from the process in the kidney of these animals in which tubular hyperplasia and microadenomas with litt le evidence of progression are the major lesions.