Mesenchymal Folliculin Defects as a Novel Pathogenic Mechanism of Polycystic Kidney Lesions
Abstract
Polycystic kidney disease (PKD) is one of the most common genetic diseases, which leads to kidney failure and other severe complications. The pathogenic mechanisms remain largely unknown. Previous studies have found that multiple genetic mutations are involved in hereditary PKD with either autosomal dominant or autosomal recessive pattern, which affect the renal epithelial cells as the primary driver of cystogenesis. Interestingly, polycystic kidney lesions are also seen in patients with BirtHogg-Dub (BHD) syndrome, which is a genetic disease caused by loss of function mutations in FLCN gene. In this project, we plan to determine whether Flcn deficiency in distinct subsets of renal mesenchymal cells leads to polycystic kidney lesions through a unique mechanism. In the past year, we have generated two different mouse lines in which Flcn is deleted in kidney mesenchymal cells using Dermo1-Cre and Foxd1-Cre drivers, respectively. The Dermo1-Cre-driven Flcn knockout results in renal polycystic lesions within two weeks after birth, while Foxd1-Cre-driven Flcn knockout does not cause kidney cysts. Kidney tissues from these two knockout mice have been harvested at different ages and their cellular and molecular differences are analyzed using a variety of cell and molecular biology approaches.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2022
- Accession Number
- AD1176319
Entities
People
- Wei Shi
Organizations
- Children's Hospital Los Angeles