Animal models of fetal renal disease

Abstract

Fetal models of urinary tract disease have been used for many years and have provided unique and important insights into the pathophysiology of these conditions. This review will summarize the principal model systems used and the current directions of investigation. These models (including rabbit, opossum, sheep and recently swine) have demonstrated that in utero obstruction of the urinary tract alters renal growth, differentiation and produces stereotypical patterns of tissue response, particularly fibrosis. New molecular understanding of these processes has identified specific mechanisms that may be key elements in the development of renal dysfunction due to obstruction. These factors include the renin-angiotensin system (RAS) and its interaction with TGF-beta in altering growth regulation and tissue fibrosis. These factors offer the prospect of clinical utility as markers of disease progression as well as pharmacologic therapy. Gene knockout systems have opened a new horizon of molecular models of congenital obstructive uropathy with insights into the role of the RAS in particular. It remains to be defined how closely these knockouts represent the human conditions they resemble. Continued application of fetal models of urinary obstruction, integrating large animal and knockout systems offers promise for improved diagnosis and treatment in these challenging conditions.