Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice.
Mutations in the retinal degeneration, retinal degeneration slow(/peripherin) and rhodopsin genes cause photoreceptor degeneration in humans and mice. Although the phenotypes arising from these mutations are different, suggesting different mechanisms of pathogenesis, we present evidence that apoptosis may be the final common pathway of the disease process linking genotype to phenotype. We observed internucleosomal cleavage of retinal DNA by gel electrophoresis and fragmented DNA at the single cell level by labeling the nicked DNA ends with biotinylated poly(dU). In retinal degeneration mice, DNA fragmentation occurred during the period of photoreceptor degeneration. In retinal degeneration slow mice and in transgenic mice expressing a mutant (Pro347Ser) rhodopsin gene, DNA fragmentation occurred after normal histogenetic cell death (also apoptosis) had ceased. Since DNA fragmentation by internucleosomal cleavage is a cardinal feature of apoptosis, our data suggest that all three of these genetic mutations lead to apoptosis.
Duke Scholars
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Related Subject Headings
- Rhodopsin
- Retinal Degeneration
- Retina
- Photoreceptor Cells
- Neurology & Neurosurgery
- Mutagenesis, Site-Directed
- Microscopy, Electron
- Mice, Mutant Strains
- Mice, Inbred C57BL
- Mice
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Rhodopsin
- Retinal Degeneration
- Retina
- Photoreceptor Cells
- Neurology & Neurosurgery
- Mutagenesis, Site-Directed
- Microscopy, Electron
- Mice, Mutant Strains
- Mice, Inbred C57BL
- Mice