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Spatial and Temporal Expression Patterns of EDA2R, PCDH9, and TRAF7 in Yotari (Dab1-/-) Mice: Implicationsfor

Jelena Komić1, Nela Kelam2, Anita Racetin2

  • 1Department of Family Medicine, Split-Dalmatia County Health Center, 21000 Split, Croatia.

International Journal of Molecular Sciences
|July 12, 2025
PubMed

Insights

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of kidney disease. This study links Reelin-Dab1 signaling to CAKUT by examining EDA2R, PCDH9, and TRAF7 protein expression in mice, finding TRAF7 plays a critical role.

Area of Science:

  • Developmental Biology
  • Genetics
  • Nephrology

Background:

  • Congenital anomalies of the kidney and urinary tract (CAKUT) represent a significant public health concern, being the third most common congenital anomaly.
  • CAKUT is the leading cause of chronic renal disease in pediatric populations and a major indication for kidney replacement therapy in both children and adults.
  • Previous research has identified candidate genes like EDA2R, PCDH9, and TRAF7 as potential contributors to CAKUT, with dysregulated protein expression noted in prior studies.

Purpose of the Study:

  • To investigate the expression patterns of EDA2R, PCDH9, and TRAF7 proteins in yotari (Dab1-/-) mice.
  • To ascertain the potential correlation between Reelin-Dab1 signaling and the expression of these candidate CAKUT-associated proteins.
  • To analyze molecular and morphological changes related to protein expression during embryonic and postnatal development in the context of CAKUT.

Main Methods:

  • Utilized yotari (Dab1-/-) mice as a model system.
  • Examined protein expression at embryonic stages (E13.5, E15.5) and postnatal stages (P4, P14).
  • Performed molecular and morphological analyses to assess protein expression patterns and their localization (cortex vs. medulla).

Main Results:

  • All three proteins (EDA2R, PCDH9, TRAF7) showed the highest expression at embryonic day 13.5 (E13.5), with a subsequent decline into postnatal stages.
  • Observed distinct differences in protein expression between the renal cortex and medulla in yotari mice compared to wild-type controls.
  • A statistically significant difference in TRAF7 expression area percentage was noted at E13.5, suggesting a direct link to Reelin-Dab1 signaling.

Conclusions:

  • The study indicates a correlation between Reelin-Dab1 signaling and the expression of EDA2R, PCDH9, and TRAF7.
  • TRAF7 protein expression patterns suggest a critical role in the pathophysiology of congenital anomalies of the kidney and urinary tract.
  • These findings provide new insights into the molecular mechanisms underlying CAKUT and highlight potential therapeutic targets.
Keywords:
CAKUTEDA2RPCDH9TRAF7kidney developmentyotari

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