A strong genetic determinant of hyperoxia-related retinal degeneration on mouse chromosome 6.
OBJECTIVE
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.
Smit-McBride
Zeljka
Z
Department of Ophthalmology, Vitreoretinal Research Lab, University of California at Davis, School of Medicine, Davis, California 95616, USA.
Oltjen
Sharon L
SL
Lavail
Matthew M
MM
Hjelmeland
Leonard M
LM
D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D018496:Hyperoxia / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000633:toxicity; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology
D010100:Oxygen