Periodic Reporting for period 1 - xenCAKUT (CRISPR/Cas9 based kidney disease modeling to elucidate novel genetic drivers and therapeutic targets in X. tropicalis)
Okres sprawozdawczy: 2020-10-01 do 2022-09-30
Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) collectively refer to a diverse group of malformations occurring during embryonic kidney and urinary tract development which underlie a major percentage (40%) of paediatric end-stage renal disease (ESRD) cases. CAKUT is also significant contributing factor to chronic kidney disease (CKD) in adults. CKD is becoming an increasing challenge for the European healthcare systems as it is estimated that between 3.3% and 17.3% of the EU population has reduced kidney function and is at high risk of becoming dependent on renal replacement therapies. In xenCAKUT, we intended to yield insight in the genetics of kidney disease using the amphibian animal model xenopus tropicalis.
Using genome editing techniques we generated new animal models for autosomal polycystic kidney disease (ADPKD). Further, we established pipelines for automated analysis of cystogenesis in these models using deep learning artificial intelligence (AI) approaches. These novel models have yielded significant new insights into ADPKD pathogenesis and were used to assess the involvement of potential modifier genes. Results where disseminated by publications in specialized scientific journals (Such as Development)
ADPKD represents the most common monogenetic disease (incidence 1:500-1:1000) and is a frequent cause of end-stage renal disease (ESRD). The xenCAKUT project achieved significant progress beyond the state of the art, establishing novel animal models for ADPKD and the AI tools to analyze these further. Together, these can lead the way towards novel treatment strategies for ADPKD.