A collaboration between LMDB and the Laboratory of Immunology at the NEI resulted in the development of transgenic mice and rats with constitutive expression of IFN-gamma in their eyes. This ongoing collaboration allowed us to study how constitutive expression of IFN- gamma and its induction and activation of IFN-gamma- inducible transcriptional factors in the eye altered the developmental fate of cells destined to become lens fiber cells by altering the pattern of lens gene expression. Another collaboration, with Baylor College of Medicine, allowed us to develop transgenic mice with ectopic expression of fibroblast growth factor (FGF)-3 in their lenses, with premature differentiation of lens central epithelia, which resulted in lens expulsion from the eye. Taken together, the results obtained with both transgenes indicate that perturbation of lens gene transcription by ectopic activation of protein kinases involved in signal transduction and the aberrant activation of transcription factors and the aberrant activation of transcription factors results in altered eye differentiation.
