Gene expression analysis of the development of congenital hydrocephalus in the H-Tx rat.

To discover candidate genes in the pathogenesis of congenital hydrocephalus, gene arrays were utilized to analyze transcripts from the midbrain region of 5-day-old H-Tx rats; these animals develop hydrocephalus due to closure of their cerebral aqueduct between embryonic day 18 and post-natal day 5. Of the 15,924 transcripts assayed, we detected 47 differentially expressed transcripts representing 23 genes and 24 expressed sequence tags (ESTs); 17 transcripts (7 genes and 10 ESTs) were upregulated and 30 (16 genes and 14 ESTs) were downregulated in the hydrocephalic animals relative to control non-hydrocephalic animals. Seven of these genes, Cck, Nfix, Lgals3, Gsta1, Xdh, Tnf, and Tfpi-2, can be linked to hydrocephalus. In addition, 17 genes that displayed altered expression in our study are not currently known to be associated with the presence or development of hydrocephalus. These results indicate that a relatively few number of transcripts were found to be altered in the development of hydrocephalus in this model. This is the first experiment of its kind to identify changes in gene expression in a congenital model of rodent hydrocephalus that are occurring locally in the area surrounding the cerebral aqueduct. Studies are now needed to examine these candidate genes and their cognate proteins to delineate their role in hydrocephalus.