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.
authors.affiliation: Center for Molecular and Human Genetics, Sections of Nephrology, Nationwide Children's Hospital, Columbus, Ohio 43205, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ingraham
authors.forename: Monalee
authors.initials: M
authors.lastname: Saha
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Carpenter
authors.forename: Melissa
authors.initials: M
authors.lastname: Robinson
authors.forename: Ihab
authors.initials: I
authors.lastname: Ismail
authors.forename: Sunita
authors.initials: S
authors.lastname: Singh
authors.forename: David
authors.initials: D
authors.lastname: Hains
authors.forename: Michael L
authors.initials: ML
authors.lastname: Robinson
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hirselj
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Koff
authors.forename: Carlton M
authors.initials: CM
authors.lastname: Bates
authors.forename: Kirk M
authors.initials: KM
authors.lastname: McHugh
mesh_terms: D000818:Animals; D002648:Child; D003559:Cystostomy; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D006801:Humans; D006869:Hydronephrosis / Q000150:complications / Q000151:congenital* / Q000473:pathology* / Q000601:surgery; D007668:Kidney / Q000000981:diagnostic imaging / Q000293:injuries* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000151:congenital* / Q000209:etiology / Q000473:pathology* / Q000601:surgery; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009395:Nephritis, Interstitial / Q000150:complications / Q000151:congenital* / Q000473:pathology* / Q000601:surgery; D014463:Ultrasonography