Retarding photoreceptor degeneration in Pdegtm1/Pdegtml mice by an apoptosis suppressor gene.

PURPOSE

Mice (Pdegtm1/Pdegtm1) homozygous for a mutant allele of the gamma subunit of retinal cyclic guanosine monophosphate phosphodiesterase (PDE gamma) suffer a severe photoreceptor degeneration. To determine whether the antiapoptotic BCL2 gene is effective in delaying the cell death pathway in this new strain of mutant mice, a transgene encoding the BCL2 gene product was introduced by mating into the mutant background, and the resulting mice were examined for possible rescue of the retinal degeneration.

METHODS

Electroretinograms (ERGs) of the Pdegtm1/Pdegtm1 mice carrying BCL2 were taken to monitor the responses to light. Light and electron microscopy of sections were used to examine degeneration at different times after birth.

RESULTS

The ERGs of the mutants with the transgene were larger than those without the transgene at 2 and 3 weeks after birth. The maximum differences occurred at 2 weeks postpartum. At 4 weeks after birth, no ERG could be detected in either strain. Histologic analysis showed a greater preservation of photoreceptor nuclei in the Pdegtm1/Pdegtm1 mice containing the BCL2 transgene, which paralleled the electroretinography.

CONCLUSIONS

The introduction of an antiapoptotic transgene BCL2 can delay temporarily and partially the degeneration of photoreceptors in a new autosomal-recessive murine model of retinal degeneration.