Pathogenesis of Renal Injury in the Megabladder Mouse: A Genetic Model of Congenital Obstructive Nephropathy

Congenital obstructive nephropathy (CON) is the most common cause of chronic renal failure in children often leading to end-stage renal disease. The megabladder ( mgb ) mouse exhibits signs of urinary tract obstruction in utero resulting in the development of hydroureteronephrosis and progressive re...

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Veröffentlicht in:Pediatric research 2010-12, Vol.68 (6), p.500-507
Hauptverfasser: Ingraham, Susan E, Saha, Monalee, Carpenter, Ashley R, Robinson, Melissa, Ismail, Ihab, Singh, Sunita, Hains, David, Robinson, Michael L, Hirselj, Daniel A, Koff, Stephen A, Bates, Carlton M, McHugh, Kirk M
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container_end_page 507
container_issue 6
container_start_page 500
container_title Pediatric research
container_volume 68
creator Ingraham, Susan E
Saha, Monalee
Carpenter, Ashley R
Robinson, Melissa
Ismail, Ihab
Singh, Sunita
Hains, David
Robinson, Michael L
Hirselj, Daniel A
Koff, Stephen A
Bates, Carlton M
McHugh, Kirk M
description Congenital obstructive nephropathy (CON) is the most common cause of chronic renal failure in children often leading to end-stage renal disease. The megabladder ( mgb ) mouse exhibits signs of urinary tract obstruction in utero resulting in the development of hydroureteronephrosis and progressive renal failure after birth. This study examined the development of progressive renal injury in homozygous mgb mice ( mgb−/− ). Renal ultrasound was used to stratify the disease state of mgb− / − mice, whereas surgical rescue was performed using vesicostomy. The progression of renal injury was characterized using a series of pathogenic markers including alpha smooth muscle isoactin (α-SMA), TGF-β1, connective tissue growth factor (CTGF), E-cadherin, F4/80, Wilm's tumor (WT)-1, and paired box gene (Pax) 2. This analysis indicated that mgb− / − mice are born with pathologic changes in kidney development that progressively worsen in direct correlation with the severity of hydronephrosis. The initiation and pattern of fibrotic development observed in mgb− / − kidneys appeared distinctive from previous animal models of obstruction. These observations suggest that the mgb mouse represents a unique small animal model for the study of CON.
doi_str_mv 10.1203/PDR.0b013e3181f82f15
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Urinary tract diseases ; Pediatric Surgery ; Pediatrics ; Ultrasonography ; Urinary system involvement in other diseases. Miscellaneous ; Urinary tract. 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The megabladder ( mgb ) mouse exhibits signs of urinary tract obstruction in utero resulting in the development of hydroureteronephrosis and progressive renal failure after birth. This study examined the development of progressive renal injury in homozygous mgb mice ( mgb−/− ). Renal ultrasound was used to stratify the disease state of mgb− / − mice, whereas surgical rescue was performed using vesicostomy. The progression of renal injury was characterized using a series of pathogenic markers including alpha smooth muscle isoactin (α-SMA), TGF-β1, connective tissue growth factor (CTGF), E-cadherin, F4/80, Wilm's tumor (WT)-1, and paired box gene (Pax) 2. This analysis indicated that mgb− / − mice are born with pathologic changes in kidney development that progressively worsen in direct correlation with the severity of hydronephrosis. The initiation and pattern of fibrotic development observed in mgb− / − kidneys appeared distinctive from previous animal models of obstruction. 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Urinary tract diseases</subject><subject>Pediatric Surgery</subject><subject>Pediatrics</subject><subject>Ultrasonography</subject><subject>Urinary system involvement in other diseases. Miscellaneous</subject><subject>Urinary tract. 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subjects Animals
basic-science-investigation
Biological and medical sciences
Child
Cystostomy
Disease Models, Animal
Disease Progression
Fibrosis
General aspects
Humans
Hydronephrosis - complications
Hydronephrosis - congenital
Hydronephrosis - pathology
Hydronephrosis - surgery
Kidney - diagnostic imaging
Kidney - injuries
Kidney - pathology
Kidney Failure, Chronic - congenital
Kidney Failure, Chronic - etiology
Kidney Failure, Chronic - pathology
Kidney Failure, Chronic - surgery
Kidneys
Male
Medical sciences
Medicine
Medicine & Public Health
Mice
Mice, Knockout
Mice, Mutant Strains
Nephritis, Interstitial - complications
Nephritis, Interstitial - congenital
Nephritis, Interstitial - pathology
Nephritis, Interstitial - surgery
Nephrology. Urinary tract diseases
Pediatric Surgery
Pediatrics
Ultrasonography
Urinary system involvement in other diseases. Miscellaneous
Urinary tract. Prostate gland
title Pathogenesis of Renal Injury in the Megabladder Mouse: A Genetic Model of Congenital Obstructive Nephropathy
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