A NEW approach for characterizing mouse urinary pathophysiologies
| Autor: | Teresa T Liu, Douglas W. Strand, Chad M. Vezina, Gervaise H. Henry, Hannah Ruetten, William A. Ricke, Heidi Spratt |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
business.industry Physiology Urinary system Urology Diuresis Male mice Urination Urine Original Articles Phenome animal models Bladder outlet obstruction Urodynamics urinary frequency Physiology (medical) parasitic diseases bladder outlet obstruction spontaneous void spot assay Etiology Medicine QP1-981 Original Article diabetic diuresis business |
| Zdroj: | Physiological Reports, Vol 9, Iss 15, Pp n/a-n/a (2021) Physiological Reports |
| Popis: | The void spot assay (VSA) is a cost‐effective method for evaluating and quantifying mouse urinary voiding phenotypes. The VSA has been used to differentiate voiding behaviors between experimental groups, but not as a diagnostic assay. To build toward this goal, we used the VSA to define voiding patterns of male mice with diabetic diuresis (BTBR.Cg‐Lep ob /WiscJ mice), irritative urinary dysfunction (E. coli UTI89 urinary tract infection), and obstructive urinary dysfunction (testosterone and estradiol slow‐release implants) compared to their respective controls. Many studies compare individual VSA endpoints (urine spot size, quantity, or distribution) between experimental groups. Here, we consider all endpoints collectively to establish VSA phenomes of mice with three different etiologies of voiding dysfunction. We created an approach called normalized endpoint work through (NEW) to normalize VSA outputs to control mice, and then applied principal components analysis and hierarchical clustering to 12 equally weighted, normalized, scaled, and zero‐centered VSA outcomes collected from each mouse (the VSA phenome). This approach accurately classifies mice based on voiding dysfunction etiology. We used principal components analysis and hierarchical clustering to show that some aged mice (>24 m old) develop an obstructive or a diabetic diuresis VSA phenotype while others develop a unique phenotype that does not cluster with that of diabetic, infected, or obstructed mice. These findings support use of the VSA to identify specific urinary phenotypes in mice and the continued use of aged mice as they develop urinary dysfunction representative of the various etiologies of LUTS in men. Our findings support continued use of the void spot assay for etiologic and therapeutic testing in mice and demonstrates for the first time that the void spot assay is not only sensitive enough to detect differences from controls but also separate different types of voiding dysfunction. Our findings also suggest that aged mice develop urinary dysfunction consistent with the range of etiologies in men and supports their use as an ideal animal model in LUTS research. This work opens the door to future studies combining VSA data with other anatomical and physiological endpoints, increasing the power of future multivariate analysis, and facilitating model building for diagnostic urinary physiology assays in mice. |
| Databáze: | OpenAIRE |
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