Transcriptional profiling of the megabladder mouse: A unique model of bladder dysmorphogenesis

Abstract

Recent studies in our lab identified a mutant mouse model of obstructive nephropathy designated mgb for megabladder. Homozygotic mgb mice (mgb؊/؊) develop lower urinary tract obstruction in utero due to a lack of bladder smooth muscle differentiation. This defect is the result of a random transgene insertion/translocation into chromosomes 11 and 16. Transcriptional profiling identified a significantly over-expressed cluster of gene products located on the translocated fragment of chromosome 16 including urotensin II-related peptide (Urp), which was shown to be preferentially over-expressed in developing mgb؊/؊ bladders. Pathway analysis of mgb microarray data indicated dysregulation of at least 60 gene products associated with smooth muscle development. In conclusion, the results of this study indicate that the molecular pathways controlling normal smooth muscle development are severely altered in mgb؊/؊ bladders, and provide the first evidence that Urp may play a critical role in bladder smooth muscle development. Developmental Dynamics 237:170 -186, 2008.

Urinary Tract Effects of HPSE2 Mutations

“…These results argue against a primary myogenic defect, as is present in the previously reported megabladder mutant mouse. 27 In turn, this supports the conclusion that the HPSE2 gene product is necessary for peripheral neural control of bladder function. Heparanase 2 deficiency during Xenopus embryogenesis increases phospho-ERK (pERK), 12 so we immunoprobed mouse pelvic ganglia for pERK (Supplemental Figure 4).…”

3‐dimensional morphometric analysis of murine bladder development and dysmorphogenesis

“…Prior studies support this hypothesis and indicate that E15 mgb −/− bladders possess high levels of apoptosis within the mesenchymal compartment, a fact that may account for the progressive loss of smooth muscle cells and total bladder volume in these animals (Singh et al, 2007). These results are consistent with prior data indicating that short axis patterning is normal in mgb −/− bladders (Singh et al, 2007; Singh et al, 2008). …”

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

“…The URP gene is overexpressed in a mouse model of obstructive nephropathy called "megabladder," which results from lack of bladder smooth muscle differentiation (Singh et al, 2008), suggesting that URP may play a critical role in bladder smooth muscle development. In frog, UII produces a concentration-dependent increase in the frequency of contraction of bladder strips (Yano et al, 1994).…”