Alterations in Bladder Function Associated With Urothelial Defects in Uroplakin II and IIIa Knockout Mice

Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Neurourology and Urodynamics (Impact Factor: 2.87). 11/2009; 28(8):1028-33. DOI: 10.1002/nau.20688
Source: PubMed


The effects of deleting genes encoding uroplakins II (UPII) and III (UPIIIa) on mouse bladder physiology/dysfunction were studied in male and female wild type and knockout (KO) mice.
UPII, UPIIIa, and WT mice were catheterized using previously described techniques. Continuous cystometry was conducted in conscious, freely moving animals. Bladder strips were harvested after animal sacrifice and pharmacological studies and EFS were conducted in an organ chamber. Histological studies were also carried on with H&E staining to identify differences among the three mouse types.
These studies have revealed numerous alterations, some of which were apparently gender-specific. Nonvoiding contractions were common in both UPII and UPIIIa KO mice, although more severe in the former. In particular, the increased bladder capacity, micturition pressure and demonstrable nonvoiding contractions observed in the male UPII KO's, were reminiscent of an obstruction-like syndrome accompanied by evidence of emerging bladder decompensation, as reflected by an increased residual volume. Pharmacological studies revealed a modest, gender-specific reduction in sensitivity of isolated detrusor strips from UPII KO female mice to carbachol-induced contractions. A similar reduction was observed in UPIIIa KO female mice. Histological investigation showed urothelial hyperplasia in both UPII KO and UPIIIa KO mice, although again, apparently more severe in the former.
These results confirm and extend previous work to indicate that urothelial defects due to uroplakin deficiency are associated with significant alterations in bladder function and further highlight the importance of the urothelium to bladder physiology/dysfunction.

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    • "Dashed gray arrows permeability of apical membrane and endocytic vesicles membrane. Knockout animals lacking the UPII or UPIIIa showed and increased permeability to urea and water (Hu et al. 2000, 2001, 2002; Kong et al. 2004; Schönfelder et al. 2006; Sun 2006; Aboushwareb et al. 2009). Furthermore, we demonstrated that, once endocytosed, the endocytic vesicles can release their content to the cytosol, depending on their differential lipid membrane composition (Grasso and Calderón 2009; Grasso et al. 2011b) Histochem Cell Biol control vesicles. "
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    Histochemie 04/2013; 140(5). DOI:10.1007/s00418-013-1095-8 · 3.05 Impact Factor
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    • "The spontaneous bladder contraction activity value for all male and female UP KO mice is significantly greater than that observed in the wild-type mice [40]. Furthermore, the UP II KO mice display significant elevations in spontaneous activity, intermicturition pressure, and micturition pressure relative to both the wild-type and UP IIIa KO mice [40]. The UP IIIa KO mice, in turn, have lower basal pressure and threshold pressure values than do either the UP II or wild-type mice [40]. "
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    • "As well as providing a barrier, the urothelial cells of the bladder also act as mechanosensors and are actively involved in triggering neural responses in response to bladder expansion. The importance of the urothelium in this process was recently highlighted by the presence of urothelial hyperplasia and non-voiding contractions in bladders from mice defective for either uroplakin II or IIIa (Aboushwareb et al, 2009). The genital tubercle (GT) gives rise to the male and female external genitalia (penis, clitoris, scrotum, labia, foreskin) and represents the intersection between the reproductive and urinary tracts. "
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