471 / 492
ICCS S5: NEUROPATHIC BLADDER
Moderators: Mario de Genarro (Italy) & Eliane Fonseca (Brazil)
ICCS Meeting on Friday 16, October 2015, 13:20 - 14:15
13:20 - 13:26
ICCS S5-1
(LO)
A MOUSE MODEL OF OCHOA SYNDROME WITH DYSFUNCTIONAL URINATION
Sean LI
1
, Chunming GUO
1
, Satoshi KANEKO
1
, Ye SUN
1
and Israel VLODAVSKY
2
1) Boston Children's Hospital, Urology, Boston, USA - 2) Rappaport Faculty of Medicine, Cancer and Vascular Biology
Research Center, Haifa, ISRAEL
PURPOSE
Genetic basis of urinary incontinence is poorly defined. Ochoa syndrome is a rare autosomal recessive disorder with
severe dysfunctional urination including megacystis, incontinence and urinary tract infection. Two candidate genes,
Hpse2 and Lrig2, have been reported but the causative role is yet to be established.
MATERIAL AND METHODS
We have generated Hpse2 and Lrig2 mouse mutants. Potential urinary tract defects were evaluated at gross,
histological, molecular and physiological levels. For example, immmunohistochemical analyses of phospho-histone H3,
smooth muscle actin and uroplakin were used to evaluate cell proliferation and differentiation defects. Voiding behavior
was examined by voided stain on paper and cystometrogram assays.
RESULTS
Deletion of Hpse2 but not Lrig2 causes megacystis and abnormal voiding behavior. While Hpse2 is largely dispensable
for development, the mutants have decreased levels of cell proliferation. Excessive amount of fibrotic bladder tissue was
observed, which correlates well with the elevated Tgfβ signaling. Hpse2 mutants leak constantly and have a significantly
higher resting intravesical pressure and maximum intravesical pressure. Comprehensive blood chemistry and urinalysis
demonstrate renal dysfunction of Hpse2 mutants.
CONCLUSIONS
We have established the first mouse genetic model, Hpse2 mutation, of Ochoa syndrome with dysfunction urination.
Hpse2 but not Lrig2 is most likely a causative gene of Ochoa syndrome. Future characterization of Hpse2 gene functions
would shed new insight onto the pathogenesis of dysfunctional urination including UI.