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Series GSE32586 Query DataSets for GSE32586
Status Public on Nov 29, 2012
Title Transcriptomic and metabolomic analysis of autosomal dominant polycystic kidney disease identifies HNF4α as a disease modifier
Organism Mus musculus
Experiment type Expression profiling by array
Summary Autosomal Dominant Polycystic Kidney Disease (ADPKD; MIM ID’s 173900, 601313, 613095) leads to end stage kidney disease, caused by mutations in PKD1 or PKD2. Inactivation of Pkd1 before or after P13 in mice results in distinct early- or late-onset disease. Using a mouse model of ADPKD carrying floxed Pkd1 alleles disrupted using a tamoxifen-inducible Cre recombinase, transcriptomics and metabolomics were applied to follow disease progression in animals induced before P10. Network analysis suggests that Pkd1-cystogenesis does not cause developmental arrest and occurs in the context of gene networks similar to those that regulate/maintain normal kidney morphology/function. These analyses also predict metabolic pathways, notably those controlled by HNF4α, are key elements in postnatal kidney maturation and early steps of cyst formation. To test this hypothesis, metabolic networks were altered by inactivating Hnf4a and Pkd1. The Pkd1/Hnf4a double knock-out have significantly more cystic kidneys thus indicating that modulating metabolic pathways might be an effective therapeutic approach.
 
Overall design We crossed fifth-generation C57/BL6 Pkd1cond mice to fifth-generation C57/BL6 tamoxifen-Cre (B6.Cg-Tg(Cre/Esr1)5Amc/J mice (stock 004682), Jackson Laboratories) and C57/BL6 congenic B6.129S4-Gt(ROSA)26Sortm1Sor/J (stock 003474, Jackson Laboratories) to produce Pkd1 conditional mice with TamCre (mutant) or without TamCre (control). We induced Cre recombinase activity in mice < 10 days of age by intraperitoneally injecting nursing mothers with tamoxifen (10 mg/40 g) , and harvested kidney samples of control and mutant (34 and 36 animals, respectively) between the ages of 11 and 24 days.

Postprocessed files (expression p value<0.05; quantile normalized; merged and corrected for batch-effect using COMBAT) linked below as supplementary files.
 
Contributor(s) Menezes LF, Germino GG
Citation(s) 23209428
Submission date Oct 04, 2011
Last update date Jun 14, 2018
Contact name Luis Fernando Menezes
E-mail(s) luis.menezes@nih.gov
Organization name National Institutes of Health
Department NIDDK
Street address Room 8D12A, Building 10, 10 Center Dr
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (2)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
GPL8540 Illumina MouseRef8 Ver1.1
Samples (70)
GSM807664 N_H17_I8_a1331_M
GSM807665 N_H17_I8_a1332_F
GSM807666 P_H17_I8_a1335_M
Relations
BioProject PRJNA147083

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE32586_LM4_LM5_LM6_LM8merged_postprocessed_forAnalysis.txt.gz 2.5 Mb (ftp)(http) TXT
GSE32586_LM4_non-normalized.txt.gz 5.7 Mb (ftp)(http) TXT
GSE32586_LM5_LM6_LM8merged_postprocessed_forAnalysis.txt.gz 3.3 Mb (ftp)(http) TXT
GSE32586_LM5_non-normalized.txt.gz 3.2 Mb (ftp)(http) TXT
GSE32586_LM6_non-normalized.txt.gz 4.6 Mb (ftp)(http) TXT
GSE32586_LM8_non-normalized.txt.gz 7.5 Mb (ftp)(http) TXT
GSE32586_LM8_postprocessed_forAnalysis.txt.gz 1.7 Mb (ftp)(http) TXT
GSE32586_RAW.tar 3.1 Mb (http)(custom) TAR
Raw data are available on Series record
Processed data included within Sample table
Processed data are available on Series record

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