Characterization of a transgenic mouse line lacking photoreceptor development within the ventral retina.
A unique transgenic mouse line was generated by incorporating a minigene that contained a cone-specific human cone transducin alpha-subunit (GNAT2) promoter, an attenuated diphtheria toxin A (DTA) gene, and an enhancer element from human interphotoreceptor retinoid-binding protein (IRBP) gene. This transgenic mouse line is designated h-GNAT2pro-DTA. During postnatal retinal development, both transgenic and non-transgenic retinas showed similar morphology and thickness at P1. Between ages P8 and P30, all retinal layers became recognizable in non-transgenic and also in transgenic dorsal retinas. However, in the ventral retina of the transgenic mice the photoreceptor layers did not develop. This aberration occurred as a result of abnormal cellular development, rather than as a consequence of retinal degeneration. In adult transgenic animals, approximately 44% of the retina located dorsally appeared morphologically normal, whereas 32% of the retina located ventrally was completely lacking photoreceptor development. The 24% mid-retinal region exhibited transitional morphology containing malformed photoreceptors. At P360 or older, the thickness of retina layers was reduced in both dorsal and ventral regions. The abnormality observed in transgenic retinas involved mainly the photoreceptors; the other retinal cell types were all present in both dorsal and ventral retinas. Since the DTA gene was only expressed in cone cells, the absence of cone photoreceptors in the transgenic retina was to be expected. However, what was unexpected was the concomitant absence of rod photoreceptors in the ventral retina, suggesting that the presence of cones may be important for the development of rods. This new transgenic line can lead to better understanding of photoreceptor development, and may serve as a new animal model for studying photoreceptor-related retinal diseases.
Fong
Shao-Ling
SL
Department of Ophthalmology, Indiana University, 702 Rotary Circle, Indianapolis, IN 46202, USA. sfong@iupui.edu
Criswell
Mark H
MH
Belecky-Adams
Teri
T
Fong
Wei-Bao
WB
McClintick
Jeanette N
JN
Kao
Winston W
WW
Edenberg
Howard J
HJ
D000818:Animals; D004167:Diphtheria Toxin / Q000235:genetics; D015870:Gene Expression; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000235:genetics; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D012160:Retina / Q000002:abnormalities / Q000254:growth & development / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000235:genetics; D015293:Transducin / Q000235:genetics; D014785:Vision, Ocular / Q000235:genetics
D004167:Diphtheria Toxin; D010446:Peptide Fragments; D012177:Retinol-Binding Proteins; C029795:diphtheria toxin fragment A; D015293:Transducin