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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
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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.
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Overall design |
We measured RNA expression by RNA-seq in control Mta2flx/flx and mutant Six2Cre Mta2flx/flx E17 kidneys.
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Contributor(s) |
Basta J, Brennan M, Rauchman M |
Citation missing |
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Submission date |
Oct 31, 2023 |
Last update date |
Nov 05, 2023 |
Contact name |
Jeannine M Basta |
E-mail(s) |
jbasta@wustl.edu
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Organization name |
Washington University in St. Louis
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Department |
Internal Medicine/Nephrology
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Lab |
Rauchman
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Street address |
660 S Euclid Ave, MSC 8126-0012-08
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City |
St. Louis |
State/province |
MO |
ZIP/Postal code |
63110 |
Country |
USA |
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Platforms (1) |
GPL18635 |
Ion Torrent Proton (Mus musculus) |
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Samples (6)
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This SubSeries is part of SuperSeries: |
GSE246695 |
Deletion of NuRD component Mta2 in nephron progenitor cells causes developmentally programmed FSGS |
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Relations |
BioProject |
PRJNA1034137 |