2,8-dihydroxyadenine nephrolithiasis induces developmental stage-specific alterations in gene expression in mouse kidney
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Updated: Jun 17, 2026
Quantitative Real-Time PCR Evaluation of microRNA Expressions in Mouse Kidney with Unilateral Ureteral Obstruction
Published on: August 27, 2020
Jianmin Chen1, Yanping Chen, Stephanie Capizzi
1Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA.
Objectives:
To identify factors that may be crucial for the initiation and progression of stone-induced injury in the developing mouse kidney by a prospective observational study using microarray analysis. Kidney stone diseases are common in premature infants, but the underlying molecular and cellular mechanisms are not fully defined.
Methods:
Mice with adenine phosphoribosyltransferase deficiency develop 2,8-dihydroxyadenine (DHA) nephrolithiasis. The gene expression changes between Aprt(-/-) and Aprt(+/+) kidneys from newborn and adult mice were compared using Affymetrix gene chips. Targets of interest were further analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry.
Results:
We identified a set of genes that were differentially expressed in the developing kidney in response to DHA-induced injury. In 1-week-old Aprt(-/-) mice, the expression of Sprr2f and Clu was highly augmented and that of Egf was significantly decreased. We also observed that maturation-related gene expression changes were delayed in developing Aprt(-/-) kidneys, and immature Aprt(-/-) kidneys contained large numbers of intercalated cells that were blocked from terminal differentiation.
Conclusions:
This study presents a comprehensive picture of the transcriptional changes induced by DHA stone injury in the developing mouse kidney. Our findings help explain growth impairment in kidneys subject to injury during the early stages of development.
Insights
Kidney stone injury in developing mice reveals delayed maturation and altered gene expression, impacting kidney growth. This study identifies key factors in stone-induced kidney damage during early development.
Area of Science:
- Nephrology
- Developmental Biology
- Genomics
Background:
- Kidney stone diseases (nephrolithiasis) are prevalent in premature infants.
- The molecular and cellular mechanisms of stone-induced kidney injury in developing kidneys are not fully understood.
Purpose of the Study:
- To identify crucial factors for the initiation and progression of stone-induced injury in developing mouse kidneys.
- To elucidate the transcriptional changes associated with 2,8-dihydroxyadenine (DHA) nephrolithiasis in the developing kidney.
Main Methods:
- A prospective observational study utilizing microarray analysis in adenine phosphoribosyltransferase-deficient (Aprt(-/-)) mice.
- Comparison of gene expression between Aprt(-/-) and wild-type (Aprt(+/+)) kidneys from newborn and adult mice.
- Validation of key gene targets using quantitative real-time polymerase chain reaction and immunohistochemistry.
Main Results:
- Identification of differentially expressed genes in response to DHA-induced kidney injury.
- Observed significant augmentation of Sprr2f and Clu, and decreased Egf expression in 1-week-old Aprt(-/-) mice.
- Delayed kidney maturation and blocked terminal differentiation of intercalated cells in developing Aprt(-/-) kidneys.
Conclusions:
- The study provides a comprehensive overview of transcriptional changes induced by DHA stone injury in the developing mouse kidney.
- Findings help explain growth impairment in kidneys injured during early developmental stages.
- Highlights the impact of early-life kidney injury on developmental trajectories.
