Lois J Arend
Johns Hopkins University, USA
Title: Novel roles for PKD genes in the reproductive tract and in stromal cells of the kidney
Biography
Biography: Lois J Arend
Abstract
Autosomal dominant polycystic disease (ADPKD) is a very common genetic disease, affecting up to 1 in 500 people. Many affected individuals progress to end-stage renal disease (ESRD) by the fifth to sixth decade of life. Mutations in the Pkd1 gene account for over 85% of ADPKD cases, while the Pkd2 gene is believed responsible for the remainder. Despite this wellestablishedrngenetic basis, current mouse models do not adequately explain the clinical progress or reveal underlying pathogenic mechanisms in human ADPKD. Many of these models have been used as the basis for developing therapeutic strategies that have failed to produce results in subsequent clinical trials.rnWe have used novel approaches to investigate the renal and reproductive tract abnormalities in mice, opening new avenuesrnfor understanding PKD and its associated morbidities. Infertility and reproductive tract abnormalities in male ADPKD patientsrnare very common and have higher incidence than in the general population. In mouse models we developed, we identify novelrndefects in the reproductive tract that could form the basis for some of these issues. In addition, a mouse model targeting Pkd1rngene deletion in the stromal cells of the kidney offers a more faithful reproduction of human ADPKD than currently availablernmodels. In particular, these mice are being used to investigate the hypothesis that a “third hit” occurs during childhood or earlyrnadulthood leading to faster, more vigorous, or larger cyst development and greater risk of progression to ESRD.The study of ADPKD has stagnated due to a lack of models that reproduce the human condition for understanding pathogenesis, progression, and targeting therapies. These models may provide new mechanistic understanding of ADPKD and hold promise as a foundation for new therapeutic strategies.