GAMMA-INTERFERON EXPRESSION DISRUPTS LENS AND RETINAL DIFFERENTIATIONIN TRANSGENIC MICE

We previously generated an animal model for the study of autoimmune di seases of the eye by targeting gamma interferon (gamma IFN) expression to the lens of transgenic mice. Here, we have studied the effect of c onstitutive lens expression of gamma IFN on eye development of these t ransgenic mice. By Day 18 of embryonic development, lens and retinal d ifferentiation programs are completely disrupted; normal lens epitheli a and fibers are replaced by balloon-like cells and retinal differenti ation into inner and outer neuroblastic layers is already affected. Th e mRNA levels of gamma E- and/or gamma F-crystallin and MIP, markers o f lens cell differentiation, are drastically reduced, while expression of ICSBP, a gamma IFN-inducible transcriptional factor, is induced in the alpha ACry-gamma IFN transgenic mouse eyes. Taken together, our r esults suggest that constitutive expression of gamma IFN and its induc tion and activation of gamma IFN-inducible transcriptional factors in the eye altered the developmental fate of cells destined to become len s fiber cells by altering the pattern of lens gene expression. (C) 199 4 Academic Press, Inc.