Conditional deletion of β1‐integrin from urothelium results in bladder dysfunction and abnormal voiding

Integrins link cells to each other and to the extracellular matrix and function to transduce physical and sensory information from the environment into biochemical signals. We used Cre‐LoxP conditional targeting to delete β1‐integrin specifically from the urothelium in mice (β1‐cKOs). Urothelium lacking integrins was morphologically normal and maintained barrier function, however these animals were incontinent with excess urine leakage ( P <0.05 for non‐corner urine spot number and spot volume). Bladder filling cystometry confirmed that β1‐cKOs exhibited excess contractility and longer voiding intervals with males having more severe symptoms than females. ATP secretion into the lumen of the bladder during filling was two‐fold greater in male β1‐cKOs than controls ( P <0.05) suggesting a purinergic signaling defect. Preliminary qPCR performed on laser‐captured urothelium suggested that female controls may have more β1‐integrin than males and that knock‐down in females may be less than complete; providing an explanation for gender differences. β1‐integrin immunolocalized to the basal/intermediate cells of the urothelium and we speculate it may be part of the mechanosensory apparatus that communicates information on bladder fullness to sensory afferents. These data demonstrate that urothelium plays an essential role in regulating voiding function. Supported by NIH grant DK083299 to WGH.