English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Urofacial syndrome (UFS) is an autosomal recessive disease with severe dysfunctional urination including urinary incontinence (UI). Biallelic mutations of  HPSE2  are discovered from UFS patients, suggesting that  HPSE2  is a candidate disease gene. Here, we show that deletion of  Hpse2  is sufficient to cause the UFS-like phenotype in mice.  Hpse2  knockout mutants display a distended bladder (megacystis) phenotype and abnormal voiding behavior similar to that found in patients. While  Hpse2  is largely dispensable for detrusor smooth muscle and urothelial cell fate determination, the mutants have significantly lower rates of cell proliferation than wild-type littermate controls. All  Hpse2  mutants have a growth retardation phenotype and die within a month after birth. Comprehensive blood chemistry and urinalysis indicate that  Hpse2  mutants have renal dysfunction and malnutrition. We provide evidence that transforming growth factor beta ( Tgfβ ) signaling is attenuated at birth. However, Tgfβ activity is significantly enhanced at later stages when the urological phenotype is severe, and the mutant bladders have accumulated excessive amount of fibrotic tissue. Together, these findings strongly suggest that  Hpse2  is a causative gene of human UFS and further uncover unexpected roles of  Hpse2  in bladder physiology, tissue remodeling and  Tgfβ  signaling.

A mouse model of urofacial syndrome with dysfunctional urination