Identification of a Unique Transgenic Mouse Line That Develops Megabladder, Obstructive Uropathy, and Renal Dysfunction

Abstract

Urinary tract malformations, obstructive uropathy, and hypoplasia/dysplasia are extremely important in terms of pediatric health care costs, with end-stage renal failure in children estimated to cost >$15 billion annually in the United States alone. Even so, little is known regarding the mechanisms that control these processes. Identified was a unique mutant mouse model that develops in utero megabladder, resulting in variable hydroureteronephrosis and chronic renal failure secondary to obstructive uropathy. These animals, designated mgb for megabladder, possess a primary defect in bladder smooth muscle development that is apparent by embryonic day 15. The mgb mouse represents an excellent model for the study of normal and pathogenic bladder development, including the postnatal progression of chronic renal failure that results from the development of in utero obstructive uropathy.

Congenital Obstructive Nephropathy: Clinical Perspectives and Animal Models

“…Megabladder mice closely mirror the pathophysiology associated with a lower urinary tract obstruction in several key respects (Ingraham, et al, 2010;Singh, et al, 2007). Mgb-/-mice develop a functional obstruction of the lower urinary tract that leads to hydroureteronephrosis during embryogenesis.…”

“…Our laboratory has identified a unique transgenic mouse model of congenital obstructive nephropathy designated the megabladder (mgb) mouse (Ingraham et al, 2010;Singh et al, 2007). As shown in Figure 7, these mice develop a nonfunctional, over-distended bladder due to a bladder-specific defect in smooth muscle differentiation.…”

Current perspectives on congenital obstructive nephropathy

“…Although mgb-/-mice do not possess PUV, the most common cause of bilateral CON in humans, the mice closely mirror the pathophysiology associated with a lower urinary tract obstruction [92,93]. First, mgb-/-mice develop a nonanatomic functional obstruction of the lower urinary tract in utero, resulting in the development of hydroureteronephrosis during late embryogenesis.…”

Osteocrin – Beyond just another bone protein?

“…Other existing models may also be useful to help demonstrate a possible role for Ostn in the skeleton. One is the "megabladder" mouse [17,18] in which embryonic expression of Ostn was found to be elevated fourfold as a result of a duplication of a locus on chromosome 16 containing the Ostn gene. The developmental bladder defect of the megabladder mouse, however, is not caused by Ostn but to the overexpression of a neighboring gene called urotensin II-related peptide.…”