Functional models for congenital anomalies of the kidney and urinary tract

Area of Science:

• Developmental biology
• Genetics
• Nephrology

Background:

• Congenital anomalies of the kidney and urinary tract (CAKUT) are common developmental diseases with largely unknown causes.
• Next-generation sequencing has identified numerous candidate genes for CAKUT, necessitating functional validation.
• Understanding the genetic basis of CAKUT is crucial for diagnosis and treatment.

Purpose of the Study:

• To review and compare different model systems used for studying CAKUT candidate genes.
• To evaluate the advantages and disadvantages of cellular, animal, and human models for functional characterization.
• To provide insights into selecting appropriate models for CAKUT research.

Main Methods:

• Review of existing literature on model systems for CAKUT gene research.
• Comparative analysis of cellular, animal (e.g., zebrafish, mouse), and human (e.g., organoids, patient-derived cells) models.
• Discussion of model system relevance and throughput for genetic variant assessment.

Main Results:

• Cellular models offer high throughput but limited physiological relevance.
• Animal models provide greater physiological relevance but lower throughput.
• Human models, including organoids, offer the highest relevance but face challenges in throughput and standardization.

Conclusions:

• No single model system is ideal for all aspects of CAKUT gene research.
• A combination of different model systems is often necessary for comprehensive functional characterization.
• Advancements in model systems are critical for deciphering the genetic etiology of CAKUT and improving patient care.