Abstract: PUB208
A Novel Genetic Model of Cystic Kidney Disease in the Mouse
Session Information
Category: Genetic Diseases of the Kidneys
- 1001 Genetic Diseases of the Kidneys: Cystic
Authors
- Waitzman, Joshua S., Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
- Onay, Ummiye venus, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
- Quaggin, Susan E., Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
Background
Polycystic kidney disease is the most common genetic cause of chronic kidney disease and end stage renal disease. While mutations in PKD1 and PKD2 cause most cases of autosomal dominant PKD, other genetic factors are thought to act as modifiers.
Methods
Using an ENU mutagenesis screen, we have identified a cystic kidney mutant that is transmitted in an autosomal dominant manner. We have characterized the mutation using both whole genome sequencing and RNA sequencing.
Results
Mice heterozygous for the trait develop glomerular and tubular cysts all along the nephron, but otherwise appear healthy. Mice that are homozygous for the trait develop hypoplastic, cystic kidneys, and are perinatally lethal with pulmonary hemorrhage. We have performed whole genome sequencing and identified potentially causative gene mutations on mouse chromosome 6. We have also performed RNA sequencing on kidneys from affected mice and matched controls and have identified significant changes in gene expression.
Conclusion
We present a novel mouse model of cystic kidney disease, which we have genetically and phenotypically characterized. We propose that the differentially regulated genetic elements that we have identified may represent genetic modifiers of cystic kidney disease.
Funding
- NIDDK Support