Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism in hyposulfatemic NaS1 null mice

Physiological Genomics
Paul Anthony DawsonDaniel Markovich

Abstract

Sulfate plays an essential role in human growth and development, and its circulating levels are maintained by the renal Na+-SO42- cotransporter, NaS1. We previously generated a NaS1 knockout (Nas1-/-) mouse, an animal model for hyposulfatemia, that exhibits reduced growth and liver abnormalities including hepatomegaly. In this study, we investigated the hepatic gene expression profile of Nas1-/- mice using oligonucleotide microarrays. The mRNA expression levels of 92 genes with known functional roles in metabolism, cell signaling, cell defense, immune response, cell structure, transcription, or protein synthesis were increased (n = 51) or decreased (n = 41) in Nas1-/- mice when compared with Nas1+/+ mice. The most upregulated transcript levels in Nas1-/- mice were found for the sulfotransferase genes, Sult3a1 (approximately 500% increase) and Sult2a2 (100% increase), whereas the metallothionein-1 gene, Mt1, was among the most downregulated genes (70% decrease). Several genes involved in lipid and cholesterol metabolism, including Scd1, Acly, Gpam, Elov16, Acsl5, Mvd, Insig1, and Apoa4, were found to be upregulated (> or = 30% increase) in Nas1-/- mice. In addition, Nas1-/- mice exhibited increased levels of hepatic lipid (appro...Continue Reading

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Citations

Feb 8, 2011·Archivum Immunologiae Et Therapiae Experimentalis·Daniel Markovich
Nov 7, 2013·Pflügers Archiv : European journal of physiology·Daniel Markovich
Jun 1, 2013·Reproduction : the Official Journal of the Society for the Study of Fertility·Paul Anthony Dawson
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Jun 10, 2011·Experimental Gerontology·Daniel MarkovichDzaidenny Muslim
Nov 10, 2009·Cancer Science·Paul Anthony DawsonGraham Robert Leggatt
May 8, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kathleen G BarrettMelissa Runge-Morris
May 16, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kathleen G BarrettMelissa Runge-Morris
Apr 15, 2011·American Journal of Physiology. Renal Physiology·Daniel Markovich
Dec 29, 2019·Pharmacological Reviews·Tina SchumannAndreas L Birkenfeld
Sep 16, 2008·The Journal of Steroid Biochemistry and Molecular Biology·Paul Anthony DawsonDaniel Markovich

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