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J Am Soc Nephrol. 2014 Jul;25(7):1440-52. doi: 10.1681/ASN.2013040390. Epub 2014 Feb 7.

MicroRNA-17~92 is required for nephrogenesis and renal function.

Author information

1
Division of Nephrology, Department of Pediatrics.
2
Department of Cell Biology.
3
Department of Pathology, and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
4
Departments of Developmental Biology and Computational Systems Biology, University of Pittsburgh School of Medicine, and.
5
Division of Nephrology, Department of Pediatrics, jacqueline.ho2@chp.edu.

Abstract

Deletion of all microRNAs (miRNAs) in nephron progenitors leads to premature loss of these cells, but the roles of specific miRNAs in progenitors have not been identified. Deletions in the MIR17HG cluster (miR-17~92 in mice), detected in a subset of patients with Feingold syndrome, represent the first miRNA mutations to be associated with a developmental defect in humans. Although MIR17HG is expressed in the developing kidney, and patients with Feingold syndrome caused by MYCN mutations have renal anomalies, it remains unclear to what extent MIR17HG contributes to renal development and function. To define the role of miR-17~92, we generated mice with a conditional deletion of miR-17~92 in nephron progenitors and their derivatives. The nephron progenitor population was preserved in these mice; however, this deletion impaired progenitor cell proliferation and reduced the number of developing nephrons. Postnatally, mutant mice developed signs of renal disease, including albuminuria by 6 weeks and focal podocyte foot process effacement and glomerulosclerosis at 3 months. Taken together, these data support a role for this miRNA cluster in renal development, specifically in the regulation of nephron development, with subsequent consequences for renal function in adult mice.

KEYWORDS:

genetic renal disease; genetics and development; nephron

PMID:
24511118
PMCID:
PMC4073423
DOI:
10.1681/ASN.2013040390
[Indexed for MEDLINE]
Free PMC Article
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