@article{sommer_estrada_collins_bedell_alexander_yang_hughes_mir_gilger_grob_et al._2011, title={Production of ELOVL4 transgenic pigs: a large animal model for Stargardt-like macular degeneration}, volume={95}, ISSN={0007-1161}, url={http://dx.doi.org/10.1136/bjophthalmol-2011-300417}, DOI={10.1136/bjophthalmol-2011-300417}, abstractNote={Background Truncation mutations in the elongation of very long chain fatty acids-4 (AF277094, MIM #605512) (ELOVL4) gene cause Stargardt-like macular dystrophy type 3 (STGD3). Mice expressing truncated ELOVL4 develop rapid retinal degeneration, but are poor STGD3 models since mice lack a macula. Photoreceptor topography in the pig retina is more similar to that in humans as it includes the cone rich, macula-like area centralis. The authors generated transgenic pigs expressing human disease-causing ELOVL4 mutations to better model the pathobiology of this macular disease. Methods Pronuclear DNA microinjection and somatic cell nuclear transfer were used to produce transgenic pigs for two different ELOVL4 mutations: the 5 base pair deletion (5 bpdel) and the 270 stop mutation (Y270terEYFP). Retinal transgene expression, morphology and electrophysiology were examined. Results The authors obtained four lines of Y270terEYFP and one line of 5 bpdel transgenic animals. Direct fluorescence microscopy indicated that the Y270terEYFP protein is expressed in photoreceptors and mislocalised within the cell. Immunohistochemical examination of transgenic pigs showed photoreceptor loss and disorganised inner and outer segments. Electroretinography demonstrated diminished responses in both transgenic models. Conclusions These transgenic pigs provide unique animal models for examining macular degeneration and STGD3 pathogenesis.}, number={12}, journal={British Journal of Ophthalmology}, publisher={BMJ}, author={Sommer, J. R. and Estrada, J. L. and Collins, E. B. and Bedell, M. and Alexander, C. A. and Yang, Z. and Hughes, G. and Mir, B. and Gilger, B. C. and Grob, S. and et al.}, year={2011}, month={Aug}, pages={1749–1754} }
 @article{petters_alexander_wells_collins_sommer_blanton_rojas_hao_flowers_banin_et al._1997, title={Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa}, volume={15}, ISSN={["1087-0156"]}, DOI={10.1038/nbt1097-965}, abstractNote={Patients with retinitis pigmentosa (RP) typically develop night blindness early in life due to loss of rod photoreceptors. The remaining cone photoreceptors are the mainstay of their vision; however, over years or decades, these cones slowly degenerate, leading to blindness. We created transgenic pigs that express a mutated rhodopsin gene (Pro347Leu). Like RP patients with the same mutation, these pigs have early and severe rod loss; initially their cones are relatively spared, but these surviving cones slowly degenerate. By age 20 months, there is only a single layer of morphologically abnormal cones and the cone electroretinogram is markedly reduced. Given the strong similarities in phenotype to that of RP patients, these transgenic pigs will provide a large animal model for study of the protracted phase of cone degeneration found in RP and for preclinical treatment trials.}, number={10}, journal={NATURE BIOTECHNOLOGY}, author={Petters, RM and Alexander, CA and Wells, KD and Collins, EB and Sommer, JR and Blanton, MR and Rojas, G and Hao, Y and Flowers, WL and Banin, E and et al.}, year={1997}, month={Oct}, pages={965–970} }