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Abstract: FR-PO297

Polycystin-2 Like 1 in Renal Cyst Formation

Session Information

Category: Genetic Diseases of the Kidneys

  • 1101 Genetic Diseases of the Kidneys: Cystic


  • Mohammadi, Ario, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Jaser, Ahmad, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Dahal, Aashish, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Liang, Lydia Jane, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Zhou, Jing, Brigham and Women's Hospital, Boston, Massachusetts, United States

Polycystin-2 (PC2), encoded by PKD2 gene is a member of the transient receptor potential (TRP) family of non-selective cation channels. Mutations in PKD2 gene cause autosomal dominant polycystic kidney disease (PKD). Polycystin-L (also called polycystin-2L1, Pkd2l1) is a Ca2+-activated non-selective cation channel with high sequence identity to polycystin 2 and is permeable to Ca2+, K+ and Na+. We have previously shown that polycystin-L is expressed primary cilia of hippocampal neurons in the brain. In the kidney, PCL is detected on the primary cilium of epithelial cells similar to other members of the polycystin family.


Genetic crossing of gene-targeted mice were used to determine the resulting phenotypes. Histology, morphometric analyses and immunostaining were used to measure cystic index and cilium length.


To determine whether polycystin-L plays a role in the kidney, we inactivated polycystin-L by gene targeting. Disruption of polycystin-L led to increased hippocampal and thalamocortical excitability, however their kidneys are phenotypically normal, which is in striking contrast with Pkd2 knockout mice that develop severe polycystic kidney disease. To determine whether polycystin-L modulates polycystic kidney disease in orthologous model of ADPKD, we created Pkd2.Pkdl double knockout mice. We observed a reduction in kidney/body weight ratio and cystic index in a subset of double knockout mice. Cilia length measurements showed Pkd2.Pkdl double knockout mice have shorter cilia than Pkd2 single knockout mice.


Disruption of both PkdL and Pkd2 in mice does not worsen the PKD phenotype in Pkd2 single knockout mice. In a significant portion of mice, there is a reduction in polycystic kidney disease severity in double knockout mice when compared with that in Pkd2 single knockout mice.


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