| First Author | Rees S | Year | 2014 |
| Journal | J Am Soc Nephrol | Volume | 25 |
| Issue | 2 | Pages | 232-7 |
| PubMed ID | 24158982 | Mgi Jnum | J:244672 |
| Mgi Id | MGI:5913451 | Doi | 10.1681/ASN.2013010077 |
| Citation | Rees S, et al. (2014) Adenylyl cyclase 6 deficiency ameliorates polycystic kidney disease. J Am Soc Nephrol 25(2):232-7 |
| abstractText | cAMP is an important mediator of cystogenesis in polycystic kidney disease (PKD). Several adenylyl cyclase (AC) isoforms could mediate cAMP accumulation in PKD, and identification of a specific pathogenic AC isoform is of therapeutic interest. We investigated the role of AC6 in a mouse model of PKD that is homozygous for the loxP-flanked PKD1 gene and heterozygous for an aquaporin-2-Cre recombinase transgene to achieve collecting duct-specific gene targeting. Collecting duct-specific knockout of polycystin-1 caused massive renal cyst formation, kidney enlargement, and severe kidney failure, with a mean survival time of 2 months. In contrast, coincident collecting duct-specific knockout of polycystin-1 and AC6 (also homozygous for the floxed ADCY6 gene) markedly decreased kidney size and cystogenesis, improved renal function, reduced activation of the B-Raf/ERK/MEK pathway, and greatly increased survival. Absence of collecting duct AC6 did not alter urinary cAMP excretion or kidney cAMP concentration. In conclusion, AC6 is a key mediator of cyst formation and renal injury in a model of PKD. |
