Renal medullary gene expression in aquaporin-1 null mice.
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 analysis model, CARMA, was used to isolate the knockout effect while taking into account experimental variability associated with microarray studies. In this study 5,701 genes of the possible approximately 12,000 genes on the array were included in the ANOVA; 531 genes were identified as demonstrating a >1.5-fold up- or downregulation between the wild-type and knockout groups. We randomly selected 35 genes for confirmation by real-time PCR, and 29 of the 35 genes were confirmed using this method. The overall pattern of gene expression in the AQP1 null mice was one of downregulation compared with gene expression in the renal medullas of the wild-type mice. Heat shock proteins 105 and 94, aldose reductase, adenylate kinase 2, aldolase B, aldehyde reductase 6, and p8 were decreased in the AQP1 null mice. Carboxylesterase 3, matrilin 2, lipocalin 2, and transforming growth factor-alpha were increased in IM of AQP1 null mice. In addition, we observed a loss of vasopressin type 2 receptor mRNA expression in renal medullas 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.
McReynolds
Matthew R
MR
Department of Physiology, College of Medicine, 1501 N Campbell Ave, University of Arizona, Tucson, AZ 85724-5051, USA.
Taylor-Garcia
Katherine M
KM
Greer
Kevin A
KA
Hoying
James B
JB
Brooks
Heddwen L
HL
D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology; D001789:Blood Group Antigens; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007679:Kidney Medulla / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014667:Vasopressins / Q000494:pharmacology
C496021:Aqp1 protein, mouse; D020346:Aquaporins; D001789:Blood Group Antigens; D014667:Vasopressins; D051398:Aquaporin 1