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Absence of p53 delays apoptotic photoreceptor cell death in the rds mouse
R R Ali1, M B Reichel, N Kanuga
1Department of Molecular Genetics, Institute of Ophthalmology, University College London, UK. r.ali@ucl.ac.uk
Purpose:
This study was aimed at determining whether or not apoptotic photoreceptor cell death in a mouse model of inherited retinal degeneration is p53 dependent.
Methods:
A colony of p53-deficient rds mice were obtained by crossing homozygous rds mice with animals homozygous for a targeted disruption of the p53 gene and genotyping the offspring of the F1 cross. Both parental strains were on a BALB/c background. Age matched p53-deficient rds mice and controls (p53-deficient, rds and BALB/c mice), were sacrificed from day 1 to day 58 after birth. Eyes were paraffin-embedded and a modified terminal dUTP nick-end labeling (TUNEL) technique was used to detect the number of cells displaying DNA fragmentation within the sectioned retina. Eyes were also resin-embedded for semi-thin and ultra-thin sectioning.
Results:
The peak in photoreceptor apoptosis, which occurs at 16 days in the rds mouse, was delayed by 3 days in p53-deficient rds mice. In addition, there was also a delay in the loss of photoreceptor cells between 16 and 26 days. However, absence of p53 did not prevent retinal degeneration in the rds mouse. The number of photoreceptor cells in p53-deficient rds mice at 35 days was very similar to that in the controls.
Conclusions:
We have demonstrated that absence of p53 delays but does not prevent photoreceptor cell loss in the rds mouse. Our results provide evidence for plasticity in the mechanism by which apoptosis proceeds in retinal degeneration.
Insights
The absence of p53 delays but does not stop photoreceptor cell death in a mouse model of inherited retinal degeneration. This suggests plasticity in the apoptosis mechanisms during retinal degeneration.
Area of Science:
- Genetics
- Cell Biology
- Ophthalmology
Background:
- Inherited retinal degeneration leads to photoreceptor cell death.
- The p53 gene plays a role in apoptosis and cell cycle control.
Purpose of the Study:
- To investigate if p53-dependent pathways regulate apoptotic photoreceptor cell death.
- To determine the role of p53 in a mouse model of inherited retinal degeneration.
Main Methods:
- Generated p53-deficient rds mice by genetic crossbreeding.
- Utilized TUNEL staining to quantify DNA fragmentation in retinal cells.
- Examined retinal tissue from mice at various developmental stages.
Main Results:
- Photoreceptor apoptosis peak was delayed by 3 days in p53-deficient mice.
- Absence of p53 delayed but did not prevent photoreceptor cell loss.
- Retinal degeneration still occurred in p53-deficient rds mice.
Conclusions:
- p53 influences the timing of photoreceptor cell death but is not essential for degeneration.
- Evidence suggests alternative apoptotic pathways are involved in retinal degeneration.
- The study highlights the plasticity of apoptosis mechanisms in the retina.