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| Status |
Public on Dec 05, 2019 |
| Title |
Genetic deletion of Pax2 and Pax8 in adult mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Background: The mammalian kidneys maintain salt and water homeostasis for proper electrolyte balance and hydration. As the glomerular filtrate passes through the nephron and into the renal medulla, electrolytes, water, and urea are reabsorbed through the concerted actions of solute carrier channels and aquaporins located at various positions along the nephron and in the outer and inner medulla. Renal epithelial cells develop from Pax2 positive proliferating stem cells that suppress Pax2 expression once differentiated into mature proximal and distal tubules, but continue to express the related Pax8 protein. The collecting tubules and renal medulla are derived from a Pax2 positive ureteric bud epithelia that continue to express Pax2 and Pax8 in adult kidneys. Despite the necessity for Pax2 in renal development, functions for Pax2 or Pax8 in adult renal epithelia have not been established.
Methods: In this report, we deleted either Pax2, Pax8, or both genes in adult mice and examined the phenotypes and changes in gene expression patterns. The mechanism of Pax8 mediated activation of potential target genes was described in inner medullary collecting duct cells.
Results: Mice with induced deletions of both Pax2 and Pax8 exhibit severe polyuria that can be attributed to significant changes in the expression of solute carriers, such as the urea transporter UTA1, and aquaporins within the inner and outer medulla. Furthermore, Pax8 expression is induced by high salt in collecting duct cells and activates the UTA1 gene by recruiting a histone methyltransferase complex to the promoter.
Conclusions: These data uncover novel functions for Pax proteins, in adult renal epithelia, that are essential for retaining water and concentrating urine.
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| Overall design |
Changes in gene expression due to the loss of Pax2 and Pax8 were estimated based on RNA transcript levels in the adult kidney.
Mice homozygous for conditonal (floxed) Pax2 and Pax8 alleles were bred to Rosa26CreER mice for tamoxifen inducible activion of Cre recombinase. Adult mice were given tamoxifen and tissues were harvested 14 days post last injection.
Total RNA from Pax2/8 knockouts and controls were isolated from kidney halves. RNAs were compared by Affymetrix Mouse Gene 2.1 ST Arrays. Controls were Cre negative and given tamoxifen.
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| Contributor(s) |
Dressler GR, Higashi AY |
| Citation missing |
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| Submission date |
Dec 04, 2019 |
| Last update date |
Dec 07, 2019 |
| Contact name |
Greg Dressler |
| E-mail(s) |
dressler@umich.edu
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| Phone |
734-764-6490
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| Organization name |
University of Michigan
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| Department |
Pathology
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| Street address |
109 Zina Pitcher Drive
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| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109 |
| Country |
USA |
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| Platforms (1) |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA593517 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE141455_RAW.tar |
28.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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