Impact of Age and Sex on Bladder Function and Stum Gene Expression in C57BL/6J Mice

Maya M. Allen

Document Type

Article

Publication Date

2025

Keywords

JMG

Abstract

Bladder dysfunction has an intense emotional and economic impact on both patients and their families. However, it is alarmingly under researched and misunderstood. Currently, there are no genetic targets for bladder function. This study aims to connect bladder function, Stum expression, aging, and sex in C57BL/6J mice.

In a recent study, a gene atlas of the mouse bladder was generated using bulkRNAseq, single-cell RNAseq, single-nucleus RNAseq, and spatial transcriptomics (Visium) (bioRxiv 2021.09.20.461121). Among the novel detrusor smooth muscle (DSM) specific genes identified in this study was Stum. Stum has been found to be key in the function of proprioceptive neurons (Desai et.al., 2014). Similar proprioception cells are present in the bladder and play a role in sensing bladder pressure and therefore urination (Gonzalez et.al., 2014). In previous experiments, our lab has shown that when Stum was knocked-out, male bladder function decreased. This was not reflected in the female population. Further investigation of Stum expression and bladder function, as well as the location of Stum expression in the bladder could uncover novel information about bladder function across age and sex.

Through void spot assay (VSA) it was found that older males had lower bladder function (expressed in higher number of voids) than their younger counterparts (p=0.05), as well as females of the same age (p=0.02). Females maintained bladder function (no significant difference between age groups). RNAscope assay of bladder tissue revealed Stum to be more prevalent in the mucosa in females (p=0.0005), and more prevalent in the muscularis tissue in males (p=0.0003). qPCR analysis that old males had lower Stum expression than females of the same age (p=0.02).

The findings of this study indicate that Stum may be a sex-linked explanation for declining bladder function, and the first genetic target for bladder dysfunction therapy.

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