Differential expression of stress response genes in the H-Tx rat model of congenital hydrocephalus.
cDNA rat stress microarrays were used to test the general hypothesis that atypical gene expression patterns exist in the brains of Hydrocephalic-Texas (H-Tx) compared to normal Sprague-Dawley (SD) rats on embryonic day 18. Sixty-two percent of the 216 target transcripts were detected in at least 2 of 3 replicates, with maximum mean fold change (MFC) ratios (H-Tx:SD) in Bcl-2-related ovarian killer protein (BOK, 3.07) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha, 0.04). Five (3.73%) of the 134 detected transcripts were elevated and 20 (17.2%) were suppressed more than twofold in H-Tx. MFC ratios for stress response, cytoskeleton-motility, and intracellular transducer-effector-modulator functional classifications were elevated, while MFC ratios for transcription and apoptosis groups were suppressed in H-Tx. K-means clustering revealed several patterns of gene expression with potential biological relevance in apoptosis, intracellular transducer-effector-modulator, metabolism, cell cycle, and stress response transcripts. Multiplex RT-PCR methodology, used to corroborate the cDNA data, captured four distinct temporal expression patterns on embryonic days 16-20 (E16-E20) for HSP27, DnaJ2, HSP47, HSP60, HSP70, HIP, HSP90A, and HSP90beta. The discovery of unique chaperone/heat shock expression profiles in the embryonic brains of H-Tx and SD rats is a powerful step towards the development of novel mechanistic hypotheses in the study of hydrocephalus disorders. This is the first study to associate early stress responses with the differential expression of chaperones/heat shock protein-related genes using the H-Tx model of congenital hydrocephalus.
Morgan
Frances W
FW
Wade's Center for Hydrocephalus, Health Research Institute, Orlando Regional Healthcare System, Inc., Orlando, FL 32806, USA. frances.morgan@orhs.org
Stewart
Jennifer A
JA
Smith
Allison N
AN
Tarnuzzer
Roy W
RW
D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006849:Hydrocephalus / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009421:Nervous System Malformations / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D017510:Protein Folding; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000235:genetics
D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger