Spontaneous voiding by mice reveals strain-specific lower urinary tract function to be a quantitative genetic trait

Area of Science:

• Urology
• Genetics
• Animal Models

Background:

• Lower urinary tract (LUT) symptoms are common with aging, affecting millions globally.
• Current therapies for LUT symptoms are often ineffective due to unknown causes.
• Existing animal models for studying LUT function are frequently invasive, hindering research.

Purpose of the Study:

• To develop a simple, reproducible, quantitative, and noninvasive assay for studying lower urinary tract (LUT) function in mice.
• To investigate the heritability of voiding characteristics and identify genetic correlates of LUT symptoms.
• To establish a tool for deriving pathophysiological LUT readouts from mouse models.

Main Methods:

• A spontaneous voiding assay was developed using filter paper to record urination patterns in young female mice from eight inbred strains.
• Voiding parameters including spot number, total volume, and voiding distribution were quantified.
• Heritability was estimated using the intraclass correlation coefficient, and urodynamic characteristics were confirmed with cystometrograms.

Main Results:

• The noninvasive voiding assay demonstrated minimal within-individual and within-strain variation but significant variations between strains for all measured parameters.
• Highly significant heritability was observed for spot number (61%), percent urine in primary void (90%), and total volume (94%).
• The assay successfully identified lower urinary tract (LUT) symptoms in aged mice, a urothelial damage model, and a diuresis model.

Conclusions:

• Voiding characteristics are heritable traits, making this assay valuable for genetic studies of lower urinary tract (LUT) symptoms.
• The noninvasive assay provides a robust method for studying LUT dysfunction and its genetic underpinnings in mouse models.
• This assay can be used to derive pathophysiological readouts for various LUT conditions.