PURPOSE. Hyperoxia-related retinal degeneration (HRRD) is a model system in the mouse in which elevated oxygen levels are used to induce retinal degeneration. The hypothesis for the present study was that strain differences in HRRD susceptibility are due to allelic variants of one or more genes in the mouse genome whose human orthologues should be important targets for research and drug development. METHODS. C57BL/6J, A/J, or B.A-Chr6 mice were exposed to 75% oxygen (hyperoxia) or room air for 14 days. After death, one eye was fixed and processed for outer nuclear layer (ONL) thickness measurements. The retina and RPE/choroid were separately dissected from the fellow eye and processed for microarray analysis. Single nucleotide polymorphism (SNP) analysis for transcribed sequences from the C57BL/6J and A/J genomes was conducted using the NIH genome site. RESULTS. C57BL/6J mice developed a significant retinal degeneration in the inferior hemisphere after 14 days of hyperoxia. Under identical conditions, A/J mice exhibited only minor changes. A significant genetic effect was located on chromosome 6. SNP analysis of known transcribed sequences on chromosome 6 combined with microarray expression analysis yielded 33 candidate genes. CONCLUSIONS. A significant genetic effect of susceptibility to HRRD is located on chromosome 6. In silico analysis of transcribed sequences results in a fairly small number of candidate genes.
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