Pathogenesis of renal injury in the megabladder mouse

A genetic model of congenital obstructive nephropathy

Susan E. Ingraham, Monalee Saha, Ashley R. Carpenter, Melissa Robinson, Ihab Ismail, Sunita Singh, David Hains, Michael L. Robinson, Daniel A. Hirselj, Stephen A. Koff, Carlton M. Bates, Kirk M. McHugh

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)500-507
Number of pages8
JournalPediatric Research
Volume68
Issue number6
DOIs
StatePublished - Dec 1 2010

Fingerprint

Genetic Models
Kidney
Wounds and Injuries
Chronic Kidney Failure
Animal Models
Cystostomy
Connective Tissue Growth Factor
Hydronephrosis
Cadherins
Urinary Tract
Renal Insufficiency
Smooth Muscle
Actins
Parturition
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Ingraham, S. E., Saha, M., Carpenter, A. R., Robinson, M., Ismail, I., Singh, S., ... McHugh, K. M. (2010). Pathogenesis of renal injury in the megabladder mouse: A genetic model of congenital obstructive nephropathy. Pediatric Research, 68(6), 500-507. https://doi.org/10.1203/PDR.0b013e3181f82f15

Pathogenesis of renal injury in the megabladder mouse : A genetic model of congenital obstructive nephropathy. / 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.

In: Pediatric Research, Vol. 68, No. 6, 01.12.2010, p. 500-507.

Research output: Contribution to journalArticle

Ingraham, SE, Saha, M, Carpenter, AR, Robinson, M, Ismail, I, Singh, S, Hains, D, Robinson, ML, Hirselj, DA, Koff, SA, Bates, CM & McHugh, KM 2010, 'Pathogenesis of renal injury in the megabladder mouse: A genetic model of congenital obstructive nephropathy', Pediatric Research, vol. 68, no. 6, pp. 500-507. https://doi.org/10.1203/PDR.0b013e3181f82f15
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. / Pathogenesis of renal injury in the megabladder mouse : A genetic model of congenital obstructive nephropathy. In: Pediatric Research. 2010 ; Vol. 68, No. 6. pp. 500-507.
@article{8b3282c9bee34094a833162fb206c6d6,
title = "Pathogenesis of renal injury in the megabladder mouse: A genetic model of congenital obstructive nephropathy",
abstract = "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.",
author = "Ingraham, {Susan E.} and Monalee Saha and Carpenter, {Ashley R.} and Melissa Robinson and Ihab Ismail and Sunita Singh and David Hains and Robinson, {Michael L.} and Hirselj, {Daniel A.} and Koff, {Stephen A.} and Bates, {Carlton M.} and McHugh, {Kirk M.}",
year = "2010",
month = "12",
day = "1",
doi = "10.1203/PDR.0b013e3181f82f15",
language = "English (US)",
volume = "68",
pages = "500--507",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Pathogenesis of renal injury in the megabladder mouse

T2 - A genetic model of congenital obstructive nephropathy

AU - Ingraham, Susan E.

AU - Saha, Monalee

AU - Carpenter, Ashley R.

AU - Robinson, Melissa

AU - Ismail, Ihab

AU - Singh, Sunita

AU - Hains, David

AU - Robinson, Michael L.

AU - Hirselj, Daniel A.

AU - Koff, Stephen A.

AU - Bates, Carlton M.

AU - McHugh, Kirk M.

PY - 2010/12/1

Y1 - 2010/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=78649336455&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649336455&partnerID=8YFLogxK

U2 - 10.1203/PDR.0b013e3181f82f15

DO - 10.1203/PDR.0b013e3181f82f15

M3 - Article

VL - 68

SP - 500

EP - 507

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 6

ER -