Alterations in bladder function associated with urothelial defects in uroplakin II and IIIa knockout mice.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Aboushwareb
Tamer
T
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Zhou
Ge
G
Deng
Fang-Ming
FM
Turner
Chanda
C
Andersson
Karl-Erik
KE
Tar
Moses
M
Zhao
Weixin
W
Melman
Arnold
A
D'Agostino
Ralph
R
Sun
Tung-Tien
TT
Christ
George J
GJ
D000818:Animals; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D001743:Urinary Bladder / Q000503:physiopathology*; D060170:Uroplakin II; D060171:Uroplakin III
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C554659:Upk2 protein, mouse; D060170:Uroplakin II; D060171:Uroplakin III