Void spot assay procedural optimization and software for rapid and objective quantification of rodent voiding function, including overlapping urine spots

Wegner, Kyle A; Abler, Lisa L.; Oakes, S. G.; Mehta, Guneet S.; Ritter, Kristina; Hill, Warren G.; Zwaans, Bernadette; Lamb, Laura E.; Wang, Zunyi; Bjorling, Dale E.; Ricke, William A.; Macoska, Jill A.; Marker, Paul C.; Southard‐Smith, E. Michelle; Eliceiri, Kevin W.; Vezina, Chad M.

doi:10.1152/ajprenal.00245.2018

Cited by 47 publications

(60 citation statements)

References 42 publications

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“…The impact of bladder radiation on mouse micturition patterns was evaluated using the void spot assay, which singly houses mice for 4 hr on cages lined with filter paper to capture the pattern of spontaneous voiding (Wegner et al, ). C3H mice are destructive to the filter paper and thus their micturition patterns cannot be analyzed using this method.…”

Section: Resultsmentioning

confidence: 99%

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Radiation cystitis modeling: A comparative study of bladder fibrosis radio‐sensitivity in C57BL/6, C3H, and BALB/c mice

et al. 2020

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A subset of patients receiving radiation therapy for pelvic cancer develop radiation cystitis, a complication characterized by mucosal cell death, inflammation, hematuria, and bladder fibrosis. Radiation cystitis can reduce bladder capacity, cause incontinence, and impair voiding function so severely that patients require surgical intervention. Factors influencing onset and severity of radiation cystitis are not fully known. We tested the hypothesis that genetic background is a contributing factor. We irradiated bladders of female C57BL/6, C3H, and BALB/c mice and evaluated urinary voiding function, bladder shape, histology, collagen composition, and distribution of collagen‐producing cells. We found that the genetic background profoundly affects the severity of radiation‐induced bladder fibrosis and urinary voiding dysfunction. C57BL/6 mice are most susceptible and C3H mice are most resistant. Irradiated C57BL/6 mouse bladders are misshapen and express more abundant collagen I and III proteins than irradiated C3H and BALB/c bladders. We localized Col1a1 and Col3a1 mRNAs to FSP1‐negative stromal cells in the bladder lamina propria and detrusor. The number of collagen I and collagen III‐producing cells can predict the average voided volume of a mouse. Collectively, we show that genetic factors confer sensitivity to radiation cystitis, establish C57BL/6 mice as a sensitive preclinical model, and identify a potential role for FSP1‐negative stromal cells in radiation‐induced bladder fibrosis.

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Section: Resultsmentioning

confidence: 99%

Section: Bladder Radiation Causes a Persistent Increase In Micturitmentioning

confidence: 99%

Radiation cystitis modeling: A comparative study of bladder fibrosis radio‐sensitivity in C57BL/6, C3H, and BALB/c mice

et al. 2020

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“…The VSA procedure has been refined considerably in recent years. Methodology improvements minimize experimental bias, new software enables rigorous and unbiased assessment, 28, 30 and 12 endpoint measurements collected in this study confer a more robust and multidimensional perspective than the five or less measurements collected in prior comparisons of male and female C57BL/6J mice. 31, 33 We identified several differences between control male and female mice.…”

Section: Resultsmentioning

confidence: 99%

“…We followed the recommended guidelines of reporting VSA data. 28–30 VSA was performed in the vivarium where mice were housed one day prior to cystometry and euthanasia. Whatman grade 540 (Fisher Scientific no.…”

Section: Methodsmentioning

confidence: 99%

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Factors Driving Unique Urination Phenotypes of Male and Female 9-week-old C57BL/6J Mice

Ruetten

Wegner

Zhang

et al. 2019

Preprint

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Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of Lower Urinary Tract Symptoms (LUTS). Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomical, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically evaluated, in part because most methods that alter prostate mass also change circulating testosterone concentrations. We performed void spot assay and cystometry to establish a multi-parameter “baseline” of voiding function in intact male and female 9-week-old (adult) C57BL/6J mice. We then compared voiding function in intact male mice to that of castrate males, males (and females) treated with the steroid five alpha reductase inhibitor finasteride, or males harboring alleles (Pbsn4cre/+;R26RDta/+) that significantly reduce prostate lobe mass by depleting prostatic luminal epithelial cells. We evaluated aging-related changes in male urinary voiding. We also treated intact male, castrate male, and female mice with exogenous testosterone to determine the influence of androgen on voiding function. The three methods used to reduce prostate mass (castration, finasteride, Pbsn4cre/+; R26RDta/+) changed voiding function from baseline but in a nonuniform manner. Castration feminized some aspects of male urinary physiology (making them more like intact female) while exogenous testosterone masculinized some aspects of female urinary physiology (making them more like intact male). Our results provide evidence that circulating testosterone is responsible in part for baseline sex differences in C57BL/6J mouse voiding function while prostate lobe mass in young, healthy adult mice has a lesser influence.

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Cuprizone‐mediated demyelination reversibly degrades voiding behavior in mice while sparing brainstem reflex

Ramasamy

Hardy

Crocker

et al. 2022

J of Neuroscience Research

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Multiple sclerosis (MS) is a chronic, progressively debilitating demyelinating disease of the central nervous system (CNS). Nearly 80% of MS patients experience lower urinary tract dysfunction early in their diagnosis. This significantly affects the quality of life, and in latter stages of disease is a leading cause of hospitalization. Previously, animal models have shown that inflammatory demyelination in the CNS causes profound bladder dysfunction, but the confounding influence of systemic inflammation limits the potential interpretation of the contribution of CNS demyelination to bladder dysfunction. Since the micturition circuit has myelinated neuronal connections in the cortex, brainstem, and spinal cord, we examined alterations in bladder function in the cuprizone model characterized by demyelinating lesions in the cortex and corpus callosum that are independent of T‐cell–mediated autoimmunity. Herein, we report that a 4‐week dietary cuprizone treatment in C57Bl/6J mice induced alterations in voiding behavior with increased micturition frequency and reduced volume voided, similar to human MS bladder dysfunction. Subsequently, recovery from cuprizone treatment restored normal bladder function. Demyelination and remyelination were confirmed by Luxol Fast Blue staining of the corpus callosum. Additionally, we also determined that an 8‐week cuprizone treatment, resulting in chronic demyelination lacking spontaneous remyelination potential, is associated with an exacerbated voiding phenotype. Interestingly, while cuprizone‐induced CNS demyelination severely affected conscious (cortical) urinary behavior, the brainstem and spinal cord reflex remained unchanged, as confirmed by urethane‐anesthetized cystometry. This is the first study to show that cortical demyelination independent of inflammation can negatively impact urinary function.

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Void spot assay procedural optimization and software for rapid and objective quantification of rodent voiding function, including overlapping urine spots

Cited by 47 publications

References 42 publications

Radiation cystitis modeling: A comparative study of bladder fibrosis radio‐sensitivity in C57BL/6, C3H, and BALB/c mice

Radiation cystitis modeling: A comparative study of bladder fibrosis radio‐sensitivity in C57BL/6, C3H, and BALB/c mice

Factors Driving Unique Urination Phenotypes of Male and Female 9-week-old C57BL/6J Mice

Cuprizone‐mediated demyelination reversibly degrades voiding behavior in mice while sparing brainstem reflex

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