Polycystic kidney disease in rhesus macaques (Macaca mulatta)

Abstract

Autosomal dominant polycystic disease (ADPKD) is one of the most common monogenetic diseases in humans affecting 1 out of 1000 individuals. ADPKD is associated with mutations in chromosomal regions designated PKD1 and PKD2. A group of rhesus macaques (Macaca mulatta) presenting with symptoms that are most consistent with the human condition of ADPKD was identified in the general colony population at the Wisconsin Primate Research Center. Renal and hepatic cysts were observed in four male rhesus macaques postmortem. Analysis of pedigrees revealed a common male ancestor. Three of the males were sired and the fourth was grandsired by this common ancestor while several first generation females did not present with hepatic or renal cysts at necropsy. This suggested a genetic component in the disease. Based on the similarities between the clinical presentation of the animal’s disease and ADPKD, the genetic component was investigated. Using the predicted rhesus macaque sequence of PKD1 and PKD2, tools were constructed to sequence both genes. These genes are expressed in PBMC and have been partially sequenced in wild type rhesus macaque. Upon analysis it was found that the observed rhesus sequences correlated closely with the predicted sequence. These genetic tools will be used to identify whether mutations exist in PKD1 or PKD2 in the affected animals. Further genetic investigation into rhesus macaque polycystic kidney disease could lead to the first viable primate model for human ADPKD study. Funded by: NIH 5P51RR000167