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Roles of uroplakins in plaque formation, umbrella cell enlargement, and urinary tract diseases.

Kong XT, Deng FM, Hu P, Liang FX, Zhou G, Auerbach AB, Genieser N, Nelson PK, Robbins ES, Shapiro E, Kachar B, Sun TT - J. Cell Biol. (2004)

Bottom Line: Both knockouts also had small superficial cells, suggesting that continued fusion of uroplakin-delivering vesicles with the apical surface may contribute to umbrella cell enlargement.Both knockouts experienced vesicoureteral reflux, hydronephrosis, renal dysfunction, and, in the offspring of some breeding pairs, renal failure and neonatal death.These results highlight the functional importance of uroplakins and establish uroplakin defects as a possible cause of major urinary tract anomalies and death.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, New York University School of Medicine, New York, NY 10016, USA.

ABSTRACT
The apical surface of mouse urothelium is covered by two-dimensional crystals (plaques) of uroplakin (UP) particles. To study uroplakin function, we ablated the mouse UPII gene. A comparison of the phenotypes of UPII- and UPIII-deficient mice yielded new insights into the mechanism of plaque formation and some fundamental features of urothelial differentiation. Although UPIII knockout yielded small plaques, UPII knockout abolished plaque formation, indicating that both uroplakin heterodimers (UPIa/II and UPIb/III or IIIb) are required for plaque assembly. Both knockouts had elevated UPIb gene expression, suggesting that this is a general response to defective plaque assembly. Both knockouts also had small superficial cells, suggesting that continued fusion of uroplakin-delivering vesicles with the apical surface may contribute to umbrella cell enlargement. Both knockouts experienced vesicoureteral reflux, hydronephrosis, renal dysfunction, and, in the offspring of some breeding pairs, renal failure and neonatal death. These results highlight the functional importance of uroplakins and establish uroplakin defects as a possible cause of major urinary tract anomalies and death.

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Related in: MedlinePlus

Inactivation of the UPII gene caused ureteral obstruction. I.v. pyelogram of normal (a) and UPII knockout mice (b) established delayed excretion of contrast in the latter. c–h show the histological sections of the ureters of normal (c and e), UPII knockout (d and f), and UPIII knockout (g and h) mice. Samples were taken from proximal (c and d) or distal (e–h) ureter. Note the formation of epithelial outgrowth filling the ureteral lumen (f), sometimes forming a complete occlusion (h). B, bladder; EO, epithelial occlusion; EP, epithelial plug; K, kidney; L, lumen. Bar, 50 μm.
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fig8: Inactivation of the UPII gene caused ureteral obstruction. I.v. pyelogram of normal (a) and UPII knockout mice (b) established delayed excretion of contrast in the latter. c–h show the histological sections of the ureters of normal (c and e), UPII knockout (d and f), and UPIII knockout (g and h) mice. Samples were taken from proximal (c and d) or distal (e–h) ureter. Note the formation of epithelial outgrowth filling the ureteral lumen (f), sometimes forming a complete occlusion (h). B, bladder; EO, epithelial occlusion; EP, epithelial plug; K, kidney; L, lumen. Bar, 50 μm.

Mentions: Another possible cause of hydronephrosis is ureteral obstruction, which impedes the flow of urine from the kidney. To investigate this possibility, we performed i.v. pyelogram (IVP) by injecting 3 μl/g (of body weight) of Omnipaque into the orbital sinus, followed by serial radiography (Fig. 8, a and b). The results indicated that UPII knockout mice had a significantly delayed excretion of Omnipaque, indicating obstruction. Serial sectioning of the urinary tracts of UPII knockout mice revealed areas of the ureter with epithelial polyps or complete epithelial occlusion, which caused structural obstruction (Fig. 8, c–h; see Discussion). These results suggest that both VUR and structural and/or functional obstruction of the ureters may be responsible for the observed hydronephrosis in UPII knockout mice.


Roles of uroplakins in plaque formation, umbrella cell enlargement, and urinary tract diseases.

Kong XT, Deng FM, Hu P, Liang FX, Zhou G, Auerbach AB, Genieser N, Nelson PK, Robbins ES, Shapiro E, Kachar B, Sun TT - J. Cell Biol. (2004)

Inactivation of the UPII gene caused ureteral obstruction. I.v. pyelogram of normal (a) and UPII knockout mice (b) established delayed excretion of contrast in the latter. c–h show the histological sections of the ureters of normal (c and e), UPII knockout (d and f), and UPIII knockout (g and h) mice. Samples were taken from proximal (c and d) or distal (e–h) ureter. Note the formation of epithelial outgrowth filling the ureteral lumen (f), sometimes forming a complete occlusion (h). B, bladder; EO, epithelial occlusion; EP, epithelial plug; K, kidney; L, lumen. Bar, 50 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172608&req=5

fig8: Inactivation of the UPII gene caused ureteral obstruction. I.v. pyelogram of normal (a) and UPII knockout mice (b) established delayed excretion of contrast in the latter. c–h show the histological sections of the ureters of normal (c and e), UPII knockout (d and f), and UPIII knockout (g and h) mice. Samples were taken from proximal (c and d) or distal (e–h) ureter. Note the formation of epithelial outgrowth filling the ureteral lumen (f), sometimes forming a complete occlusion (h). B, bladder; EO, epithelial occlusion; EP, epithelial plug; K, kidney; L, lumen. Bar, 50 μm.
Mentions: Another possible cause of hydronephrosis is ureteral obstruction, which impedes the flow of urine from the kidney. To investigate this possibility, we performed i.v. pyelogram (IVP) by injecting 3 μl/g (of body weight) of Omnipaque into the orbital sinus, followed by serial radiography (Fig. 8, a and b). The results indicated that UPII knockout mice had a significantly delayed excretion of Omnipaque, indicating obstruction. Serial sectioning of the urinary tracts of UPII knockout mice revealed areas of the ureter with epithelial polyps or complete epithelial occlusion, which caused structural obstruction (Fig. 8, c–h; see Discussion). These results suggest that both VUR and structural and/or functional obstruction of the ureters may be responsible for the observed hydronephrosis in UPII knockout mice.

Bottom Line: Both knockouts also had small superficial cells, suggesting that continued fusion of uroplakin-delivering vesicles with the apical surface may contribute to umbrella cell enlargement.Both knockouts experienced vesicoureteral reflux, hydronephrosis, renal dysfunction, and, in the offspring of some breeding pairs, renal failure and neonatal death.These results highlight the functional importance of uroplakins and establish uroplakin defects as a possible cause of major urinary tract anomalies and death.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, New York University School of Medicine, New York, NY 10016, USA.

ABSTRACT
The apical surface of mouse urothelium is covered by two-dimensional crystals (plaques) of uroplakin (UP) particles. To study uroplakin function, we ablated the mouse UPII gene. A comparison of the phenotypes of UPII- and UPIII-deficient mice yielded new insights into the mechanism of plaque formation and some fundamental features of urothelial differentiation. Although UPIII knockout yielded small plaques, UPII knockout abolished plaque formation, indicating that both uroplakin heterodimers (UPIa/II and UPIb/III or IIIb) are required for plaque assembly. Both knockouts had elevated UPIb gene expression, suggesting that this is a general response to defective plaque assembly. Both knockouts also had small superficial cells, suggesting that continued fusion of uroplakin-delivering vesicles with the apical surface may contribute to umbrella cell enlargement. Both knockouts experienced vesicoureteral reflux, hydronephrosis, renal dysfunction, and, in the offspring of some breeding pairs, renal failure and neonatal death. These results highlight the functional importance of uroplakins and establish uroplakin defects as a possible cause of major urinary tract anomalies and death.

Show MeSH
Related in: MedlinePlus