Transcriptional adaptation to Clcn5 knockout in proximal tubules of mouse kidney.
Dent disease has multiple defects attributed to proximal tubule malfunction including low-molecular-weight proteinuria, aminoaciduria, phosphaturia, and glycosuria. To understand the changes in kidney function of the Clc5 chloride/proton exchanger gene knockout mouse model of Dent disease, we examined gene expression profiles from proximal S1 and S2 tubules of mouse kidneys. We found many changes in gene expression not known previously to be altered in this disease. Genes involved in lipid metabolism, organ development, and organismal physiological processes had the greatest number of significantly changed transcripts. In addition, genes of catalytic activity and transporter activity also had a great number of changed transcripts. Overall, 720 genes are expressed differentially in the proximal tubules of the Dent Clcn5 knockout mouse model compared with those of control wild-type mice. The fingerprint of these gene changes may help us to understand the phenotype of Dent disease.
Wright
Jerry
J
Department of Medicine, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Morales
Marcelo M
MM
Sousa-Menzes
Jackson
J
Ornellas
Debora
D
Sipes
Jennifer
J
Cui
Yan
Y
Cui
Isabelle
I
Hulamm
Phuson
P
Cebotaru
Valeriu
V
Cebotaru
Liudmila
L
Guggino
William B
WB
Guggino
Sandra E
SE
D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D018118:Chloride Channels / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D040181:Genetic Diseases, X-Linked; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D020133:Reverse Transcriptase Polymerase Chain Reaction
C097503:CLC-5 chloride channel; D018118:Chloride Channels