The overall objective of the proposed studies is to obtain information regarding the role of TULP1 in the retina. The applicant recently obtained evidence pointing to the TULP1 gene as a cause for autosomal recessive retinitis pigmentosa (ARRP). The protein product of this gene is specifically expressed in the retina, but little additional information regarding the function of this protein exists. RP is a hereditary blinding disorder afflicting thousands of people. The genetic etiology of RP is known for only about 20 percent of the cases and the biochemical pathways involved in causing the disease even less. The first specific aim of this application focuses on localizing TULP1 in the retina. Determining the cell type(s) expressing TULP1 will begin to give clues as to the function of the protein. Experiments designed to achieve aim one will be conducted using molecular techniques including in situ hybridization and immunohistochemistry.
The second aim i nvolves analyzing a transgenic mouse strain lacking a functional TULP1 gene. It will be important to evaluate the retina of these mice for possible pathologic changes that might correlate with those found in humans with TULP1 mutations. The last specific aim involves proving that identified defects in the TULP1 gene cause retinal degeneration. This will be done by attempting to rescue the TULP1 knock-out mice (assuming the mice degenerate) by re-introducing the wild-type gene and by generating transgenic mice expressing constructs containing known TULP1 mutations on the null background. Methods to evaluate all mice include funduscopy, light and electron microscopy, and electroretinography. Discovering information regarding the function of TULP1 will hopefully provide knowledge about pathways involved in retinal degeneration.
