Inherited pelvic organ prolapse in the mouse: preliminary evaluation of a new murine model

Abstract

The objective of this study was to report the initial anatomic, radiographic, and genetic evaluations of a novel form of spontaneous pelvic organ prolapse (S-POP) in mice. We observed S-POP in a colony of UPII-SV40T transgenic mice developed for studies on bladder cancer. We utilized magnetic resonance imaging and necropsy to characterize this finding. We have established a breeding colony to identify inheritance patterns and for future studies. Selective breeding isolated the S-POP phenotype from the transgene. In contrast to other animal models, the S-POP mouse does not require an obligatory antecedent event to manifest pelvic organ prolapse. Necropsy and imaging demonstrate significant displacement of the pelvic organs distal to the pelvic floor in both sexes. The appearance of the POP is similar to that seen in the human female phenotype. Preliminary breeding studies indicate an autosomal dominant inheritance pattern. This mouse may be an effective animal model for the study of POP in humans.

Figure 1

CT images of normal (left) and S-POP male mice (right). The mice were scanned following injection of contrast agent to aid in visualization of the urinary tract. In the normal mouse the smooth spherical object located above the pubic bones is the bladder. Above that, the contrast agent can be seen in the renal pelvi (pyramid shaped objects above the bladder). The bladder in the S-POP mouse is distal to the skeletal pelvis, and the prolapse has resulted in significant retention of contrast agent in the kidneys and ureter, consistent with hydroureter and hydronephrosis.

Figure 2

Necropsy of male S-POP mouse, proceeding Box A to Box E. The enlarged scrotum is clearly evident (A). After removal of the abdominal wall (B), the tstes were located in the abdomen (C). Extraction of the prolapsed cecum (D), and then bladder (E) empty the scrotum. The cavity through which the organs were withdrawn can be seen in Box F (yellow arrow).

Figure 3

Necropsy of female S-POP mouse. The abdominal wall is removed (B) and fat pads are evident (C). In this mouse, a segment of bowel, uterus, and the bladder were withdrawn from the prolapse (D and E).

Figure 4

MRI images of female S-POP mouse. The image on the left is a coronal slice of the three dimensional MRI dataset. The locations of the three axial slices to the right are indicated. The top slice is at the level of the renal pelvis. The dark regions in the kidney are not normal and perhaps indicative of lower urinary tract obstruction. The middle slice is at the level at which the bladder is normally positioned. The bottom slice shows the severe organ prolapse at the level of the ischia with a full bladder, displaced and compressed vagina and rectum.

Figure 5

Pedigree showing autosomal dominant inheritance of S-POP phenotype. Mouse number 1385 was selected for breeding based on exhibition of the S-POP phenotype. Mouse 1385 may be homozygous for the S-POP mutation and if so we expect all of his progeny to develop prolapse. He was mated to two FVB female mice and two litters were produced. One male mouse was found moribund shortly after weaning. Of the eight females, 6 females are exhibiting S-POP at 4 months of age. Of the 8 surviving male mice, two have developed S-POP. The evaluation is based on external examination with comparison to wildtype animals.

Figure 6

Identification of pelvic muscles in wildtype female mouse by MRI.