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Series GSE246694 Query DataSets for GSE246694
Status Public on Nov 05, 2023
Title Deletion of NuRD component Mta2 in nephron progenitor cells causes developmentally programmed FSGS [E17.RNAseq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Low nephron endowment at birth is a risk factor for chronic kidney disease. The prevalence of this condition is increasing due to higher survival rates of preterm infants and children with multi- organ birth defect syndromes that affect the kidney and urinary tract. We created a mouse model of congenital low nephron number due to deletion of Mta2 in nephron progenitor cells. Mta2 is a core component of the Nucleosome Remodeling and Deacetylase (NuRD) chromatin remodeling complex. These mice developed albuminuria at 4 weeks of age followed by focal segmental glomerulosclerosis (FSGS) at 8 weeks, with progressive kidney injury and fibrosis. Our studies reveal that altered mitochondrial metabolism in the post-natal period leads to accumulation of neutral lipids in glomeruli at 4 weeks of age followed by reduced mitochondrial oxygen consumption. We found that NuRD cooperated with Zbtb7a/7b to regulate a large number of metabolic genes required for fatty acid oxidation and oxidative phosphorylation. Analysis of human kidney tissue also supported a role for reduced mitochondrial lipid metabolism and ZBTB7A/7B in FSGS and CKD. We propose that an inability to meet the physiological and metabolic demands of post-natal somatic growth of the kidney promotes the transition to CKD in the setting of glomerular hypertrophy due to low nephron endowment.
Overall design We measured RNA expression by RNA-seq in control Mta2flx/flx and mutant Six2Cre Mta2flx/flx E17 kidneys.
Contributor(s) Basta J, Brennan M, Rauchman M
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Submission date Oct 31, 2023
Last update date Nov 05, 2023
Contact name Jeannine M Basta
Organization name Washington University in St. Louis
Department Internal Medicine/Nephrology
Lab Rauchman
Street address 660 S Euclid Ave, MSC 8126-0012-08
City St. Louis
State/province MO
ZIP/Postal code 63110
Country USA
Platforms (1)
GPL18635 Ion Torrent Proton (Mus musculus)
Samples (6)
GSM7874737 con.005
GSM7874738 mut.006
GSM7874739 con.007
This SubSeries is part of SuperSeries:
GSE246695 Deletion of NuRD component Mta2 in nephron progenitor cells causes developmentally programmed FSGS
BioProject PRJNA1034137

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Supplementary file Size Download File type/resource
GSE246694_E17.Mta2.RNAseq.Rauchman.xlsx 3.0 Mb (ftp)(http) XLSX
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Raw data are available in SRA

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