Apoptotic photoreceptor death in the rhodopsin knockout mouse in the presence and absence of c-fos.
A combined total of approximately 100 mutations have been encountered within the rhodopsin gene in retinitis pigmentosa (RP) and congenital night blindness. Mice carrying a targeted disruption of the rhodopsin gene phenotypically mimic RP, losing their photoreceptors over a period of 3 months and having no recordable rod electroretinogram. These animals will serve as a model for both recessive and dominant disease (in the latter case, the presence of normal and mutant human rod opsin transgenes on the murine Rho(-/-)background). Precise knowledge of apoptotic photoreceptor cell death, together with factors which may influence apoptosis will be required for optimum utility of Rho(-/-)mice as a model for therapeutic genetic intervention. A peak phase of apoptosis of the photoreceptors of Rho(-/-)mice was shown to occur at 24 days post-birth. The extent of apoptosis appeared to be similar, irrespective of whether or not the rod opsin knockout was present on a c-fos(+/+)or c-fos(-/-)genetic background, the latter known to favor survival of photoreceptors following exposure of mouse retinas to excessive light. These data clearly support the existence in animals of distinct apoptotic pathways in light-induced, as opposed to mutation-induced apoptosis, and together with similar observations recently reported in studies of the naturally occurring rd mouse, may assist in focusing future research on precisely defining the distinct molecular pathways giving rise to such dichotomy.
Hobson
A H
AH
The Ocular Genetics Unit, Trinity College, Dublin, 2, Ireland.
Donovan
M
M
Humphries
M M
MM
Tuohy
G
G
McNally
N
N
Carmody
R
R
Cotter
T
T
Farrar
G J
GJ
Kenna
P F
PF
Humphries
P
P
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004195:Disease Models, Animal; D016762:Genes, fos / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000503:physiopathology*; D012243:Rhodopsin / Q000235:genetics* / Q000502:physiology
D012243:Rhodopsin