TIGR AND DEVELOPMENT OF THE EYE

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Mutations in the TIGR gene are estimated to contribute to 3 percent of the total cases of open angle glaucoma, but the normal function of TIGR and the pathogenesis of TIGR-related glaucoma remain unknown. The long term objective of this project is to elucidate the roles of the TIGR gene product in eye development, with the hope that this information will provide a context within which to understand how TIGR mutations contribute to disease. The immediate goal of the work in this proposal is to develop animal systems for studying TIGR function during development. This project has three specific aims. Specific aim 1 is to obtain TIGR genomic clones from mouse and chicken tissue and to determine the patterns of TIGR expression in embryonic, neonatal, and adult eyes. Specific aim 2 is to generate two lines of transgenic mice with different disruptions in the TIGR gene and to analyze the consequences of these disruptions on eye development. Specific aim 3 tests the hypothesis that the transcription factor 1mx-b regulates TIGR expression during embryogenesis. This work will be an important first step in understanding the roles of TIGR during eye development and disease, and will be the foundation of future studies.