2004 Global Researcher Conference Proceeding

April 09 - 11, 2004

Conference: 2004 Global Researcher Conference
Title: Renal medullary gene expression in aquaporin-1 null mice
Authors: Brooks, Heddwen L.; McReynolds, Matthew R.; Garcia-Taylor, Katherine; Greer, Kevin; Hoying, James
Institution: University of Arizona
Brooks Mice that lack the aquaporin-1 gene (AQP1) lack a functional countercurrent multiplier mechanism, fail to concentrate the inner medullary (IM) interstitium and present with a urinary concentrating defect. In this study we use DNA microarrays to identify the gene expression profile of the IM of AQP1 null mice and corresponding changes in gene expression resulting from a loss of a hypertonic medullary interstitium. An ANOVA model was used to isolate the knockout effect while taking into account experimental variability associated with microarray studies (array, dye, spot). In this study 5701 genes out of the possible ~12000 genes on the array were included in the ANOVA. We considered genes to be significantly differentially expressed if the ANOVA p value was < 0.05. 531 genes were identified as demonstrating a > 1.5 fold up or down regulation between the wild type and knock-out groups. We randomly selected 32 genes for confirmation by real-time PCR and 29 of 32 were confirmed using this method. The overall pattern of gene expression in the AQP1 null mice was one of down-regulation compared to gene expression in the renal medullae of the wild type mice. Heat shock proteins 105 and 94, 3-beta hydroxysteroid dehydrogenase 4, adenylate kinase 2, aldolase B, megalin, aldehyde reductase 6 and p8 were decreased in the AQP1 null mice. Uroplakin 1A, carboxylesterase 3, matrilin 2 and lipocalin 2 were increased in IM of AQP1 null mice. In addition, we observed a loss of vasopressin type 2 receptor expression in the renal medullae of the AQP1 null mice. Thus, the loss of the hyperosmotic renal interstitium, due to a loss of the concentrating mechanism, drastically altered not only the phenotype of these animals but also their renal medullary gene expression profile (DK064706, AZ Foundation).
Mice that do not have the aquaporin-1 (AQP1) gene are unable to concentrate urine. Brooks, et al., examined mice lacking AQP1 in order to see how this affects other genes that are normally expressed in the inner medullary (IM) section of the mouse kidney. They found that, overall, mice lacking AQP1 have fewer genes expressed in the IM than normal mice. The researchers also observed that mice lacking AQP-1 did not express vasopressin-2 (V2R) in the kidney medullae. So, not only are these mice unable to concentrate urine, they also express fewer genes in their kidney medullae.