Table 2.
Evidence from animal and human studies of genes potentially involved in the pathogenesis of pelvi-ureteric junction obstruction
| Gene | Full gene name | Animal | Features and mechanism | Human | Reference |
|---|---|---|---|---|---|
| Ace | Angiotensin converting enzyme | Ace −/− mice | Hydronephrosis, renal parenchymal atrophy | [51] | |
| Adamts-1 | A disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 1 | Adamts -1−/− mice | PUJ obstruction, increased collagen at PUJ. Other urogenital anomalies. | [52] | |
| Agt | Angiotensin | Agt −/− mice | Hydronephrosis, renal parenchymal atrophy, | [53] | |
| Agtr 1a/b | Angiotensin II receptor type 1 (1a and 1b) | Agtr1 −/− (1a and 1b) mice | Hydronephrosis in older mice, renal parenchymal atrophy, failure of renal pelvis development, ureteric smooth muscle hypoplasia and abnormal peristalsis | [31] | |
| Aqp2 | Aquaporin 2 | Aqp 2S256L/S256L CPH mice | Mutation in CPH mice prevents Aqp2 phosphorylation and normal trafficking. Hydronephrosis secondary to polyuria | [54] | |
| Calcineurin | Calcineurin. Also known as Protein phosphatase 3 (ppp3) | Pax3-Cre T/+; Cnb1 flox/ flox mice | Calcineurin inactivation in metanephric and ureteral mesenchyme giving hydronephrosis, abnormal pyeloureteral peristalsis with defective renal pelvis and smooth muscle development | [30] | |
| Id2 | Inhibitor of DNA binding 2 | Id2 −/− and Id2 +/− mice | Hydronephrosis and PUJ development | [38] | |
| Nfia | Nuclear factor I/A | Nfia +/− and Nfia −/− mice | Hydroureteronephrosis, VUR, abnormal PUJ and VUJ development. CNS malformations. | Nfia +/−due to chromosomal translocation and deletion. VUR and CNS malformations. | [55] |
| TBX18 | T-box transcription factor | Tbx18 −/− mice | Hydroureteronephrosis, short ureters, ureteric smooth muscle defects due to abnormal smooth muscle cell differentiation and localisation | Hispanic family with autosomal dominant CAKUT predominantly PUJO. Heterozygous truncating mutation (c.1010delG) of Tbx18 | [24, 56] |
| Tshz2 and 3 | Teashirt zinc finger family member 2 and 3 | Tshz3 −/− mice | Hydronephrosis with PUJ configuration, abnormal smooth muscle differentiation proximal ureter | Tshz2/Tshz3 mutations not cause of PUJO in Albanian/Macedonian population | [57, 58] |
CAKUT, Congenital anomalies of the kidney and urinary tract; CNS, central nervous system; CPH, congenital progressive hydronephrosis; PUJO, pelvi-ureteric junction obstruction; VUJ, vesico-ureteric junction; VUR, vesico-ureteric reflux