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| Status |
Public on Nov 05, 2023 |
| Title |
Deletion of NuRD component Mta2 in nephron progenitor cells causes developmentally programmed FSGS [2month.ChIPseq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy 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 |
Binding of Mta2, Mbd3, and Zbtb7a to chromatin was measured by comparing specific chromatin binding to Input chromatin in 2 month old mouse kidney cortex.
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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) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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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 |
PRJNA1034138 |
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