Spatial and Temporal Expression Patterns of EDA2R, PCDH9, and TRAF7 in Yotari (Dab1−/−) Mice: Implicationsfor Understanding CAKUT Pathogenesis

Congenital anomalies of the kidney and urinary tract (CAKUT) are the third most common congenital anomaly and a significant public health concern. It is the predominant cause of chronic renal disease in pediatric populations and the principal reason for kidney replacement therapy in individuals under 20, as well as the fourth leading cause in adults. Five candidate genes, including EDA2R, PCDH9, and TRAF7 were identified as potential contributors to CAKUT. These genes had not been previously prioritized in CAKUT research, and our prior studies have demonstrated that the proteins encoded by these candidate genes display dysregulated expression across various CAKUT subgroups. Our research examined the expression patterns of EDA2R, PCDH9, and TRAF7 in yotari (Dab1−/−) mice at two embryonic stages (E13.5 and E15.5) and two postnatal stages (P4 and P14) to ascertain the potential correlation between Reelin–Dab1 signaling, previously linked to CAKUT phenotypes, and the aforementioned proteins through molecular and morphological analyses. All three observed proteins exhibited the highest area percentage at E13.5, with a trend of decline into postnatal stages, during which specific changes in protein expression were noted between the cortex and medulla of yotari mice compared to wild-type mice. For TRAF7, a statistically significant difference in area percentage at E13.5 was observed, indicating a link with Reelin–Dab1 signaling and a potentially critical role in the pathophysiology of CAKUT, also marked by our prior study.