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Renal pathogenesis in a transgenic model of in utero obstructive nephropathy
Author(s) -
McHugh Kirk M,
Singh Sunita,
Robinson Melissa,
Robinson Michael L,
Bates Carlton M
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a142-a
Subject(s) - medicine , obstructive uropathy , in utero , ctgf , pathology , urinary system , endocrinology , growth factor , biology , pregnancy , fetus , genetics , receptor
In utero obstructive nephropathy has the potential to interrupt normal renal development and represents the most common cause of chronic renal failure in children, with end‐stage renal disease costing over 15 billion dollars annually in the United States alone. We have identified a unique mutant mouse model, designated mgb for megabladder, that develops overt signs of lower urinary tract obstruction in utero resulting in the development of hydroureteronephrosis and progressive renal failure. Morphological studies indicate that homozygotic (−/−) mgb mice develop urinary tract obstruction in utero as a result of a lack of smooth muscle development within the bladder. Incipient signs of renal failure are evident in mgb−/− mice shortly after birth as marked by a significant increase in BUN and creatinine levels in conjunction with a concomitant decrease in bicarbonate levels. Immunohistochemical studies indicate that mgb−/− kidneys show an increase in the presence of a‐smooth muscle positive myofibroblasts and interstitial fibrosis as marked by collagen deposition. In addition, the expression of transforming growth factor beta (TGF‐b) and connective tissue growth factor (CTGF), a downstream target/mediator of TGF‐b induced injury, are both up‐regulated in mgb−/− kidneys. The mgb mouse represents a unique and innovative genetic model for the study of the postnatal progression of chronic renal failure resulting from the development of in utero obstructive nephropathy permitting the evaluation of genetic, surgical and pharmacological strategies designed to ameliorate this important disease process.