PAX2, a member of the PAX family of transcription factors, is essential for the development of the urinary system, along with other transcription factors. It is involved in the development processes, emergence of nephrons and collecting tubes from the seventh week of gestation [1]. PAX2 also plays a role in neurodevelopment, with its mutations associated with neurodevelopmental disorders such as intellectual disability, epilepsy, and autism spectrum disorders [2].

Mutations in the human PAX2 gene can lead to congenital anomalies of the kidneys and urinary tract (CAKUT), and in some cases, renal coloboma syndrome, which involves both renal anomalies and eye involvement [1,3]. Animal models, like the Pax2A220G/+ mouse model, have shown that Pax2 is important for glomerular repair. Mice with this missense variant have reduced nephron numbers, are more susceptible to glomerular disease after podocyte injury, and have impaired parietal epithelial cell (PEC)-mediated podocyte regeneration [4].

In summary, PAX2 is crucial for the normal development of the urinary and nervous systems. Through model-based research, especially the Pax2-related mouse models, we have gained insights into its role in kidney development, glomerular repair, and its association with diseases such as CAKUT and renal coloboma syndrome, as well as neurodevelopmental disorders.

References:

1. Muntean, Carmen, Chirtes, Camelia, Baczoni, Balazs, Banescu, Claudia. 2023. PAX2 Gene Mutation in Pediatric Renal Disorders-A Narrative Review. In International journal of molecular sciences, 24, . doi:10.3390/ijms241612737. https://pubmed.ncbi.nlm.nih.gov/37628926/

2. Lv, Na, Wang, Ying, Zhao, Min, Dong, Lina, Wei, Hongen. 2021. The Role of PAX2 in Neurodevelopment and Disease. In Neuropsychiatric disease and treatment, 17, 3559-3567. doi:10.2147/NDT.S332747. https://pubmed.ncbi.nlm.nih.gov/34908837/

3. Giovanella, Silvia, Pasini, Andrea, Ligabue, Giulia, Tagliafico, Enrico, Magistroni, Riccardo. 2022. PAX2/Renal Coloboma Syndrome Expresses Extreme Intrafamilial Phenotypic Variability. In Nephron, 147, 120-126. doi:10.1159/000525022. https://pubmed.ncbi.nlm.nih.gov/35790137/

4. Cunanan, Joanna, Rajyam, Sarada Sriya, Sharif, Bedra, John, Rohan, Barua, Moumita. 2024. Mice with a Pax2 missense variant display impaired glomerular repair. In American journal of physiology. Renal physiology, 326, F704-F726. doi:10.1152/ajprenal.00259.2023. https://pubmed.ncbi.nlm.nih.gov/38482556/