Genetic networks controlling retinal injury.
Document Type
Article
Publication Date
2005
Keywords
Animals, Brain-Injuries, Databases-Factual, Eye-Injuries, Eye-Proteins, Gene-Expression-Profiling, Gene-Expression-Regulation, Linkage-(Genetics), 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
First Page
958
Last Page
970
JAX Source
Mol Vis 2005; 11:958-70.
Abstract
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.
Recommended Citation
Vazquez CF,
Khan AN,
Chan CK,
Moore AN,
Dash PK,
Hernandez MR,
Lu L,
Chesler EJ,
Manly KF,
Williams RW,
Geisert EE.
Genetic networks controlling retinal injury. Mol Vis 2005; 11:958-70.