Neuron
Volume 11, Issue 4, October 1993, Pages 595-605
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Article
Apoptosis: Final common pathway of photoreceptor death in rd, rds, and mutant mice

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Abstract

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.

References (57)

  • A. Alles et al.

    Apoptosis: a general comment

    FASEB J.

    (1991)
  • M.J. Arends et al.

    Apoptosis: the role of the endonuclease

    Am. J. Pathol.

    (1990)
  • E.L. Berson

    Retinitis pigmentosa, the Friedenwald Lecture

    Invest. Ophthal. Vis. Sci.

    (1993)
  • C. Bowes et al.

    Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMPphosphodiesterase

    Nature

    (1990)
  • L. Carter-Dawson et al.

    Differential effect of the rd mutation on rods and cones in the mouse retinal

    Invest. Ophthal. Vis. Sci.

    (1978)
  • G.J. Chader et al.

    Studies on animal models of retinal degeneration

  • J.J. Cohen et al.

    Glucocorticoid activation of calcium dependent endonuclease in thymocyte nuclei leads to cell death

    J. Immunol.

    (1984)
  • F. Connell et al.

    Photoreceptor peripherin is the normal product of the gene responsible for retinal degeneration in the rds mouse

  • L.G. Davis et al.

    Basic Methods in Molecular Biology

    (1986)
  • T.P. Dryja et al.

    A point mutation of the rhodopsin gene in one form of retinitis pigmentosa

    Nature

    (1990)
  • T.P. Dryja et al.

    Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa

    N. Engl. J. Med.

    (1990)
  • R.C. Duke et al.

    Endogenous endonuclease induced DNA fragmentation: an early event in cell-mediated cytolysis

  • R.E. Ellis et al.

    Mechanisms and functions of cell death

    Annu. Rev. Cell Biol.

    (1991)
  • D. Farber et al.

    Cyclic guanosine monophosphate: elevation in degenerating photoreceptor cells of the C3H mouse retina

    Science

    (1974)
  • G.J. Farrar et al.

    A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa

    Nature

    (1991)
  • B.L. Finlay

    Cell death and the creation of regional differences in neuronal numbers

    J. Neurobiol.

    (1992)
  • I. Garcia et al.

    Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene

    Science

    (1992)
  • Y. Gavrieli et al.

    Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation

    J. Cell Biol.

    (1992)
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