Format

Send to

Choose Destination
Chem Biol Interact. 2017 Oct 1;276:15-22. doi: 10.1016/j.cbi.2017.02.013. Epub 2017 Feb 28.

Transcriptomic analysis and plasma metabolomics in Aldh16a1-null mice reveals a potential role of ALDH16A1 in renal function.

Author information

1
Department of Environmental Health Sciences, Yale School of Public Health, Yale School of Medicine, New Haven, CT 06520, United States.
2
Department of Environmental Health Sciences, Yale School of Public Health, Yale School of Medicine, New Haven, CT 06520, United States; College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, PR China.
3
Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 80045, United States.
4
Department of Biostatistics, Yale School of Public Health, Yale School of Medicine, New Haven, CT 06520, United States.
5
Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Center, University of Colorado, Aurora, CO, 80045, United States.
6
Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 80045, United States.
7
Department of Environmental Health Sciences, Yale School of Public Health, Yale School of Medicine, New Haven, CT 06520, United States. Electronic address: vasilis.vasiliou@yale.edu.

Abstract

ALDH16A1 is a novel member of the ALDH superfamily that is enzymatically-inactive and highly expressed in the kidney. Recent studies identified an association between a rare missense single nucleotide variant (SNV) in the ALDH16A1 gene and elevated serum uric acid levels and gout. The present study explores the mechanisms by which ALDH16A1 influences uric acid homeostasis in the kidney. We generated and validated a mouse line with global disruption of the Aldh16a1 gene through gene targeting and performed RNA-seq analyses in the kidney of wild-type (WT) and Aldh16a1 knockout (KO) mice, along with plasma metabolomics. We found that ALDH16A1 is expressed in proximal and distal convoluted tubule cells in the cortex of the kidney and in zone 3 hepatocytes. RNA-seq and gene ontology enrichment analyses showed that cellular lipid and lipid metabolic processes are up-regulated. Three transporters localized in the apical membrane of the proximal convoluted tubule of the kidney known to influence urate/uric acid homeostasis were found to be up-regulated (Abcc4, Slc16a9) or down-regulated (Slc17a3). An initial metabolomics analysis in plasma revealed an altered lipid profile in KO mice that is in agreement with our RNA-seq analysis. This is the first study demonstrating a functional role of ALDH16A1 in the kidney.

KEYWORDS:

ALDH16A1; Gene enrichment analysis; Lipid metabolism; Metabolomics; RNA-seq; Renal function

PMID:
28254523
PMCID:
PMC5725231
DOI:
10.1016/j.cbi.2017.02.013
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center