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A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction
Published on: December 20, 2014
Renal developmental genes are differentially regulated after unilateral ureteral obstruction in neonatal and adult
Melanie J Kubik1, Maja Wyczanska2, Mojca Gasparitsch2
1Department of Pediatrics, Ruprecht-Karls-University, Heidelberg, Germany.
Abstract:
Congenital obstructive nephropathy hinders normal kidney development. The severity and the duration of obstruction determine the compensatory growth of the contralateral, intact opposite kidney. We investigated the regulation of renal developmental genes, that are relevant in congenital anomalies of the kidney and urinary tract (CAKUT) in obstructed and contralateral (intact opposite) kidneys after unilateral ureteral obstruction (UUO) in neonatal and adult mice. Newborn and adult mice were subjected to complete UUO or sham-operation, and were sacrificed 1, 5, 12 and 19 days later. Quantitative RT-PCR was performed in obstructed, intact opposite kidneys and sham controls for Gdnf, Pax2, Six4, Six2, Dach1, Eya1, Bmp4, and Hnf-1β. Neonatal UUO induced an early and strong upregulation of all genes. In contrast, adult UUO kidneys showed a delayed and less pronounced upregulation. Intact opposite kidneys of neonatal mice revealed a strong upregulation of all developmental genes, whereas intact opposite kidneys of adult mice demonstrated only a weak response. Only neonatal mice exhibited an increase in BMP4 protein expression whereas adult kidneys strongly upregulated phosphatidylinositol 3 kinase class III, essential for compensatory hypertrophy. In conclusion, gene regulation differs in neonatal and adult mice with UUO. Repair and compensatory hypertrophy involve different genetic programs in developing and adult obstructed kidneys.
Insights
Neonatal unilateral ureteral obstruction (UUO) strongly upregulates kidney development genes in both affected and opposite kidneys. Adult UUO shows a weaker, delayed response, indicating age-dependent gene regulation during kidney repair and compensatory growth.
Area of Science:
- Nephrology
- Developmental Biology
- Molecular Biology
Background:
- Congenital obstructive nephropathy impairs kidney development.
- Compensatory kidney growth depends on obstruction severity and duration.
- Congenital anomalies of the kidney and urinary tract (CAKUT) involve developmental gene dysregulation.
Purpose of the Study:
- Investigate the regulation of CAKUT-relevant renal developmental genes.
- Compare gene regulation in neonatal versus adult mice after unilateral ureteral obstruction (UUO).
- Analyze gene expression in both obstructed and contralateral kidneys.
Main Methods:
- Unilateral ureteral obstruction (UUO) or sham-operation in neonatal and adult mice.
- Quantitative RT-PCR analysis of specific renal developmental genes (Gdnf, Pax2, Six4, Six2, Dach1, Eya1, Bmp4, Hnf-1β).
- Assessment at 1, 5, 12, and 19 days post-operation.
Main Results:
- Neonatal UUO caused early, strong upregulation of all studied genes in both obstructed and contralateral kidneys.
- Adult UUO showed delayed and less pronounced gene upregulation.
- Neonatal contralateral kidneys strongly upregulated developmental genes; adult contralateral kidneys showed a weak response.
- BMP4 protein increased in neonatal UUO kidneys; adult kidneys upregulated phosphatidylinositol 3 kinase class III for compensatory hypertrophy.
Conclusions:
- Gene regulation in response to UUO differs significantly between neonatal and adult mice.
- Developing and adult kidneys utilize distinct genetic programs for repair and compensatory hypertrophy following obstruction.
