a novel mouse model reveals that polycystin-1 deficiency in ependyma and choroid plexus results in dysfunctional cilia and hydrocephalus一种新的小鼠模型显示,polycystin-1室管膜、脉络丛不足导致不正常的纤毛和脑积水.pdfVIP

A Novel Mouse Model Reveals that Polycystin-1 Deficiency in Ependyma and Choroid Plexus Results in Dysfunctional Cilia and Hydrocephalus 1. 1. 1 1 2 1 Claas Wodarczyk , Isaline Rowe , Marco Chiaravalli , Monika Pema , Feng Qian , Alessandra Boletta * 1 Dulbecco Telethon Institute (DTI) at Dibit, San Raffaele Scientific Institute, Milan, Italy, 2 Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America Abstract Polycystin-1 (PC-1), the product of the PKD1 gene, mutated in the majority of cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD), is a very large (,520 kDa) plasma membrane receptor localized in several subcellular compartments including cell-cell/matrix junctions as well as cilia. While heterologous over-expression systems have allowed identification of several of the potential biological roles of this receptor, its precise function remains largely elusive. Studying PC-1 in vivo has been a challenging task due to its complexity and low expression levels. To overcome these limitations and facilitate the study of endogenous PC-1, we have inserted HA- or Myc-tag sequences into the Pkd1 locus by homologous recombination. Here, we show that our approach was successful in generating a fully functional and easily detectable endogenous PC-1. Characterization of PC-1 distribution in vivo showed that it is expressed ubiquitously and is developmentally-regulated in most tissues. Furthermore, our novel tool allowed us to investigate the role of PC-1 in brain, where the protein is abundantly expressed. Subcellular localization of PC-1 revealed strong and specific st