Generation of a transgenic rabbit model of retinal degeneration.
OBJECTIVE
To generate a transgenic (Tg) rabbit model of retinal degeneration and to characterize the pattern of degeneration by using histology and electrophysiology.


METHODS
Rhodopsin Pro347Leu Tg rabbits were generated by BAC transgenesis. Tg rabbits were identified by Southern blot analysis, 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 characteristics 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 remained at 35% in the wild-type at the same time point. The retinal ultrastructure of Tg rabbits showed a large number of small vesicles that accumulated in the extracellular space of the photoreceptors.


CONCLUSIONS
To the best of the authors' knowledge, this is the first rabbit model of progressive retinal degeneration. Because rabbits have large eyes and are easy to handle and breed, they will provide a useful animal model for the study of the pathophysiology of and new treatments for retinal degeneration.
Kondo
Mineo
M
Department of Ophthalmology, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
Sakai
Takao
T
Komeima
Keiichi
K
Kurimoto
Yukihide
Y
Ueno
Shinji
S
Nishizawa
Yuji
Y
Usukura
Jiro
J
Fujikado
Takashi
T
Tano
Yasuo
Y
Terasaki
Hiroko
H
D000818:Animals; D030801:Animals, Genetically Modified; D015139:Blotting, Southern; D022202:Chromosomes, Artificial, Bacterial; D004195:Disease Models, Animal; D004596:Electroretinography; D005451:Fluorescein Angiography; D017403:In Situ Hybridization; D017354:Point Mutation; D011817:Rabbits / Q000235:genetics*; D012160:Retina / Q000503:physiopathology / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012243:Rhodopsin / Q000235:genetics; D019076:Transgenes
D012243:Rhodopsin