Generation of a Transgenic Rabbit Model of Retinal Degeneration

¹ Department of Ophthalmology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
² Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan
³ Research Institute of Life and Health Sciences, Chubu University, Kasugai, Japan
⁴ Department of Materials Physics and Engineering, Nagoya University Graduate School of Engineering, Nagoya, Japan
⁵ Osaka University Graduate School of Medicine, Department of Applied Visual Science, Suita, Japan
⁶ Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan

^* To whom correspondence should be addressed. E-mail: kondomi{at}med.nagoya-u.ac.jp.

	Abstract

PURPOSE. To generate a transgenic (Tg) rabbit model of retinal degeneration and to characterize the pattern of degeneration using histology and electrophysiology. METHODS. Rhodopsin Pro347Leu Tg rabbits were generated using BAC transgenesis. Tg rabbits were identified by Southern blotting, and the expression levels were measured by quantitative RT-PCR. Retinal histology was examined by light and electron microscopy and immunohistochemistry. Retinal function was assessed by full-field electroretinograms (ERGs). RESULTS. Six lines of Tg rabbits were generated, and two lines with higher levels of expression showed rod-dominant progressive retinal degeneration. Retinal histology indicated a marked regional variation in the loss of photoreceptors with the central retina more severely affected than the peripheral retina. The characterisitics of the ERGs of transgenic rabbits indicated that the rod components of the ERGs were reduced to only 5% by 48 weeks, whereas the cone components still remained at 35% of the wild-type at the same time. The retinal ultrastructure of Tg rabbits showed a large number of small vesicles that accumulated in the extracellular space of the photoreceptors. CONCLUSION. To the best of our knowledge, this is the first rabbit model of progressive retinal degeneration. Because the rabbits have large eyes and are easy to handle and breed, these animals will be a useful animal model to study the pathophysiology and new treatments for retinal degeneration.

Key Words: transgenic animals, rhodopsin, retinitis pigmentosa, retinal degeneration, rabbit, bacterial artificial chromosome

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