Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Hnf4a deletion in the mouse kidney phenocopies Fanconi renotubular syndrome
Sierra S. Marable, … , S. Steven Potter, Joo-Seop Park
Sierra S. Marable, … , S. Steven Potter, Joo-Seop Park
Published July 25, 2018
Citation Information: JCI Insight. 2018;3(14):e97497. https://doi.org/10.1172/jci.insight.97497.
View: Text | PDF
Research Article Development Nephrology

Hnf4a deletion in the mouse kidney phenocopies Fanconi renotubular syndrome

  • Text
  • PDF
Abstract

Different nephron tubule segments perform distinct physiological functions, collectively acting as a blood filtration unit. Dysfunction of the proximal tubule segment can lead to Fanconi renotubular syndrome (FRTS), with major symptoms such as excess excretion of water, glucose, and phosphate in the urine. It has been shown that a mutation in HNF4A is associated with FRTS in humans and that Hnf4a is expressed specifically in proximal tubules in adult rat nephrons. However, little is known about the role of Hnf4a in nephrogenesis. Here, we found that Hnf4a is expressed in both presumptive and differentiated proximal tubules in the developing mouse kidney. We show that Hnf4a is required for the formation of differentiated proximal tubules but is dispensable for the formation of presumptive proximal tubules. Furthermore, we show that loss of Hnf4a decreased the expression of proximal tubule–specific genes. Adult Hnf4a mutant mice presented with FRTS-like symptoms, including polyuria, polydipsia, glycosuria, and phosphaturia. Analysis of the adult Hnf4a mutant kidney also showed proximal tubule dysgenesis and nephrocalcinosis. Our results demonstrate the critical role of Hnf4a in proximal tubule development and provide mechanistic insight into the etiology of FRTS.

Authors

Sierra S. Marable, Eunah Chung, Mike Adam, S. Steven Potter, Joo-Seop Park

×

Figure 1

Hnf4a is expressed in the developing nephron.

Options: View larger image (or click on image) Download as PowerPoint

Hnf4a is expressed in the developing nephron.
(A) In nascent S-shaped b...
(A) In nascent S-shaped body (SSB), Hnf4a is not detected. Representative image of n = 3. Scale bar: 25 μm. (B) Hnf4a is expressed in a subset of Jag1+ cells in the medial segment of the elongated SSB. Scale bar: 25 μm. Image is representative of n = 3. (C) Hnf4a is detected in presumptive proximal tubule (PT) cells and differentiated PT cells. Presumptive PT cells show weak Lotus tetragonolobus lectin (LTL) staining and are located more cortically, where early stages of nephrogenesis occur. Differentiated PT cells show strong LTL staining and are located closer to the medullary region. Image is representative of n = 3. Scale bar: 100 μm.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts