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A Possible Zebrafish Model of Polycystic Kidney Disease: Knockdown of wnt5a Causes Cysts in Zebrafish Kidneys
Published on: December 2, 2014
Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model
Sabrine Hassane1, Nanna Claij, Irma S Lantinga-van Leeuwen
1Center for Human and Clinical Genetics, Leiden University Medical Center, Postal zone: S-04-P, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Arteriosclerosis, Thrombosis, and Vascular Biology
|July 28, 2007
Summary
Autosomal Dominant Polycystic Kidney Disease (ADPKD) involves kidney cyst growth and serious aortic aneurysms. Our study in a Pkd1 mouse model shows polycystin1 deficiency weakens the aorta, leading to dissecting aneurysms.
Area of Science:
- Vascular Biology
- Genetics
- Nephrology
Background:
- Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder causing kidney cysts and increasing risks of intracranial and aortic aneurysms.
- Mutations in PKD1 or PKD2 genes are the primary cause of ADPKD.
- Vascular complications, particularly aortic aneurysms, represent a significant threat to ADPKD patients.
Purpose of the Study:
- To investigate the role of polycystin1 in vascular remodeling and dissecting aneurysm formation.
- To characterize the pathogenetic sequence of aortic dissecting aneurysms in a hypomorphic Pkd1 mouse model.
Main Methods:
- Analysis of vascular remodeling in a hypomorphic Pkd1(nl/nl) mouse model.
- Quantitative real-time polymerase chain reaction to assess Pkd1 gene expression in the aorta.
- (Immuno)histochemical characterization of aortic tissue.
Main Results:
- Reduced Pkd1 expression (approx. 26%) was observed in the aorta of Pkd1(nl/nl) mice.
- Pathogenesis involved matrix accumulation between elastin lamellae, increased smooth muscle cells, and media weakening.
- Intimal tears, due to matrix accumulation and endothelial cell detachment, combined with media weakness, led to intramural bleeding and vessel rupture.
Conclusions:
- Polycystin1 is crucial for maintaining the structural integrity of the aortic wall.
- The Pkd1(nl/nl) mouse model is valuable for studying the mechanisms of dissecting aneurysm formation.
