Summary
Introduction and objective
Stress urinary incontinence is of concern in both pediatric and adult population.
Double mutant GLI family zinc finger Gli2+/−; Gli3Δ699/+ murine model of stress incontinence has been recently developed as a reliable model
which does not require surgical manipulation to create incontinence and is shown to
survive to adulthood. The aim of this study was to establish the etiology of incontinence
in the double mutant Gli2+/−; Gli3Δ699/+ mice.
Study design
We used 13 cluster of differentiation 1 (CD-1) mice (7–9 weeks) for demonstration
of histology of the bladder and urethra. There were 3 Wild Gli2+/- females, 2 Wild Gli2+/- males, 4 Gli2+/-;Gli3Δ699/+ females and 4 Gli2+/-;Gli3Δ699/+ males. The Wild Gli2+/- mice served as the control group and Gli2+/-;Gli3Δ699/+ mice served as the test group. Additionally, eight 16.5 days mice (2 each of Wild
Gli2+/- females, Wild Gli2+/- males, double knockout (DKO) Gli2+/-;Gli3Δ699/+ females and Gli2+/-;Gli3Δ699/+ males) were used to assess the histology of the spinal cord. The gross appearance
of bladder and urethra was studied using ink injection assays. Immunohistochemistry
was done for smooth muscle actin and cytokeratin.
Results
Gross and histologic appearance confirmed the previously reported widening of bladder
outlet and hypoplasia of smooth muscles in female urethra and also established them
in the male urethra of Gli2+/-;Gli3Δ699/+ mice compared to Gli2+/- mice. The double knockout mice were smaller than the Gli2 mice (5.2 vs 6.1 cm, p = 0.002).
Immunohistochemistry demonstrated epithelial hyperplasia and smooth muscle hypoplasia.
Additionally, there was prostatic hypoplasia in the Gli2+/-;Gli3Δ699/+ male mice. The spinal cord length for body size appeared comparable between the Gli2+/- and Gli2+/-;Gli3Δ699/+ mice but histological evaluation revealed abnormal development of the caudal end
of the vertebral body with premature termination of the spinal cord (Figure).
Discussion
The histological changes in the bladder neck and urethra were consistent to those
previously reported. While previous report described the findings in female mice only,
we confirmed that these findings are also present in males as well as prostatic hypoplasia,
a possible additional factor leading to stress incontinence. The most important finding
in the present study however, was the detection of premature termination of spinal
cord in the DKO Gli2+/−; Gli3Δ699/+ mice which has not been reported previously and is likely a major contributor to
incontinence in this model.
Conclusion
Graphical Abstract(a) Gross appearance of the spinal cord in Gli2+/−; Gli3Δ699/+ (left side) and Gli2+/− (right side) mice showing proportional length for body size. (b) Histological evaluation
of 16.5 days Gli2+/− (left side) and Gli2+/−; Gli3Δ699/+ (right side) mice showing caudal vertebral bodies and spinal cords. Note the difference
at the caudal end (Asterisks denote attachment of tail). Scale bars: 1 mm.
Keywords
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Article info
Publication history
Published online: October 05, 2022
Accepted:
October 3,
2022
Received in revised form:
August 14,
2022
Received:
January 10,
2022
Identification
Copyright
© 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
