Genetic networks controlling retinal injury.
PURPOSE: The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury.
METHODS: A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases.
RESULTS: The acute phase response of rat retina, brain, and spinal cord was dominated by transcription factors. Three genomic loci control transcript expression of acute phase genes in brains of BXD RI mouse strains. One locus was identified on chromosome 12 and was highly correlated with the expression of classic acute phase genes. Within the locus we identified the inhibitor of DNA binding 2 (Id2) as a candidate upstream regulator. Id2 was upregulated as an acute phase transcript in injury models of rat retina, brain, and spinal cord.
CONCLUSIONS: We defined a group of transcriptional changes associated with the retinal acute injury response. Using genetic linkage analysis of natural transcript variation, we identified regulatory loci and candidate regulators that control transcript levels of acute phase genes.
Acute-Phase Proteins, Animals, Brain Injuries, Databases, Factual, Eye Injuries, Eye Proteins, Gene Expression Profiling, Gene Expression Regulation, Genetic Linkage, Meta-Analysis as Topic, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Rats, Retina, Spinal Cord Injuries, Transcription Factors, Wound Healing