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 (gamma GT) promoter. In three lines, hyperplasia developed as early as 11.5 days postconception in the outer neuroectodermal layer, which gives rise to ciliary body and retinal pigment epithelium. At birth, the eyes from many animals contained adenomas, and by day 27, mice developed invasive adenocarcinomas originating in the region of the ciliary body. Microphthalmia, cataracts, and chronic nongranulomatous inflammation involving the anterior and/or posterior segments of the eye were also found. gamma GT is detectable histochemically as early as 11.5 gestational days in the outer neuroectodermal layer and after birth is more abundant in the ciliary body than in the retinal pigment epithelium. Using a reverse transcriptase-polymerase chain reaction, we found that type I (but not types II or III) gamma GT RNA is made by the mouse eye; the gamma GT(I)rasT24 transgene transcription product was detected in the eyes of all five transgenic lines. The sequential progression of hyperplasia to invasive neoplasms in the ciliary body in response to gamma GT(I)rasT24 expression differs from the process in the kidney of these animals in which tubular hyperplasia and microadenomas with little evidence of progression are the major lesions.
Chévez-Barrios
P
P
Department of Ophthalmology, University of Texas Medical School, Houston.
Schaffner
D L
DL
Barrios
R
R
Overbeek
P A
PA
Lebovitz
R M
RM
Lieberman
M W
MW
D000230:Adenocarcinoma / Q000235:genetics; D000236:Adenoma / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D002924:Ciliary Body / Q000502:physiology*; D005123:Eye / Q000737:chemistry / Q000473:pathology*; D011905:Genes, ras; D006651:Histocytochemistry; D006965:Hyperplasia / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010857:Pigment Epithelium of Eye / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D005723:gamma-Glutamyltransferase / Q000235:genetics
D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D005723:gamma-Glutamyltransferase