Retinal degeneration in cone photoreceptor cell-ablated transgenic mice.
OBJECTIVE
To examine the effect of loss of cone photoreceptor cells on retinal degeneration.


METHODS
We previously identified a cone photoreceptor cell-specific promoter of human cone transducin a-subunit (GNAT2) gene. In this report, a minigene, Trc-Tox176, that contains the GNAT2 promoter, an attenuated diphtheria toxin A-chain gene, and an enhancer element from human interphotoreceptor retinoid-binding protein (IRBP) was used to generate coneless transgenic mice. Transgenic mice were identified by PCR and the copy number of the transgene was determined by Southern hybridization, and examined by histology.


RESULTS
The results of immunostaining with anti-mouse GNAT2 antibodies and reverse transcription-PCR (RT-PCR) analysis with mRNA from the retinas of transgenic mice showed that cone photoreceptor cells were ablated in one of four transgenic mouse lines. The ablation of cone cells began at postnatal day 8, at the same time as the expression of endogenous GNAT2. An age-related rod degeneration was also found in this cone-ablated mouse line, beginning at postnatal day 9, proceeding from the central retina to the peripheral retina.


CONCLUSIONS
Cone photoreceptor cells may play an important role in the survival of rod photoreceptor cells during mouse retina development.
Ying
S
S
Departments of Ophthalmology and Cell Biology, Neurobiology and Anatomy, University of Cincinnati, Cincinnati, OH 45267-0527, USA.
Jansen
H T
HT
Lehman
M N
MN
Fong
S L
SL
Kao
W W
WW
D000818:Animals; D015139:Blotting, Southern; D004167:Diphtheria Toxin / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012160:Retina / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015293:Transducin / Q000235:genetics / Q000378:metabolism
D004167:Diphtheria Toxin; D015293:Transducin