A NEW approach for characterizing mouse urinary pathophysiologies.

Area of Science:

• Urology
• Animal Models
• Phenotyping

Background:

• The void spot assay (VSA) is a cost-effective method for evaluating mouse urinary voiding phenotypes.
• Current VSA applications primarily differentiate experimental groups, not diagnose specific dysfunctions.
• Understanding diverse urinary dysfunction etiologies in mice is crucial for translational research.

Purpose of the Study:

• To establish comprehensive VSA phenomes for classifying mouse voiding dysfunction.
• To define voiding patterns in male mice with diabetic diuresis, urinary tract infections, or obstructive urinary dysfunction.
• To assess the utility of VSA phenomes for identifying specific urinary phenotypes and their relevance to human conditions.

Main Methods:

• Utilized VSA to collect 12 normalized, scaled, and zero-centered voiding outcomes from each mouse.
• Developed the normalized endpoint work through (NEW) approach to normalize VSA outputs relative to control mice.
• Applied principal components analysis and hierarchical clustering to the VSA phenome data for classification.

Main Results:

• The VSA phenome approach accurately classified mice based on the etiology of their voiding dysfunction.
• Diabetic, infected, and obstructed mice exhibited distinct VSA phenomes.
• Aged mice (>24 months) developed obstructive, diabetic diuresis, or unique VSA phenotypes.

Conclusions:

• The VSA phenome approach successfully identifies specific urinary phenotypes in mice across different etiologies.
• This method provides a robust tool for characterizing voiding dysfunction in preclinical models.
• Findings support the use of aged mice in studies of urinary dysfunction relevant to male lower urinary tract symptoms (LUTS).