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S. Fong, M.H. Criswell, W.W. Kao, W. Fong; Characterization of a Novel Transgenic Mouse Line Lacking Photoreceptor Development in the Inferior Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4516.
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Purpose:To characterize a new transgenic mouse line that could be used in developmental and retinal disease research. Methods:A cone photoreceptor cell-ablated transgenic mouse line was initially generated by introducing a minigene (Trc-Tox176) that contained the GNAT2 promoter, an attenuated diphtheria toxin A-chain, and an enhancer element from human IRBP (Molecular Vision 2000; 6:101-108). The original line exhibited post-natal central-to-peripheral retinal degeneration. The new mouse line appeared after cross breeding a male transgenic mouse with C57 females over several years. Successive generations of this new transgenic line have demonstrated consistent traits. Here longitudinal sections of eyes from transgenic mice (pups to adults) and nontransgenic litter mates were examined by light microscopy. Retinal gene expression levels were evaluated by RT-PCR. Results:In transgenic animals (regardless of age), ~ 44% of the nasal and temporal retina located superiorly appeared morphologically normal, whereas 32% of the inferior retina completely lacked photoreceptor development (i.e., no outer segments, ONL, or OPL), although the RPE layer remained intact. The 24% mid-retinal region exhibited transitional morphology containing partial and malformed photoreceptors. The INL in the inferior retina was thicker than that found superiorly, and may reflect embryonic cell spread into available space. Many retina-specific genes were observed by RT-PCR, including opsin, green visual pigment, GNAT1 and GNAT2 genes. Tissues from the superior retina consistently demonstrated higher expression levels compared to values obtained from the inferior retina. Conclusions:The absence of photoreceptors in the inferior retina is thought to occur through a lack of development, not from retinal degeneration. The underlying cause of this unexpected and dramatic difference in development, particularly between superior and inferior retina, remains under investigation. This new transgenic line serves a potentially useful role for studying the mechanisms of photoreceptor development and as an animal model in retinal disease research.
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