Genetic networks controlling retinal injury.
OBJECTIVE
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.
Vazquez-Chona
Felix R
FR
Department of Ophthalmology, The Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA. fvazquez@utmem.edu
Khan
Amna N
AN
Chan
Chun K
CK
Moore
Anthony N
AN
Dash
Pramod K
PK
Hernandez
M Rosario
MR
Lu
Lu
L
Chesler
Elissa J
EJ
Manly
Kenneth F
KF
Williams
Robert W
RW
Geisert
Eldon E
EE
D000209:Acute-Phase Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism; D016208:Databases, Factual; D005131:Eye Injuries / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D008040:Genetic Linkage; D015201:Meta-Analysis as Topic; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D012160:Retina / Q000293:injuries*; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics*
D000209:Acute-Phase Proteins; D005136:Eye Proteins; D014157:Transcription Factors